{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T04:54:01Z","timestamp":1781672041437,"version":"3.54.5"},"reference-count":50,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Small Methods"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Surface\u2010enhanced Raman scattering (SERS) nanoprobe\u2010based immunoassay is an emerging liquid biopsy modality for the detection of blood biomarkers. However, quantitative detection of blood biomarkers using SERS nanoprobe immunoassays remains challenging, primarily due to intrinsic stochastic fluctuations of SERS signals. Herein, Ag nanogap shells (AgNGS) encoded with Raman labels are prepared as SERS nanoprobes with single\u2010particle sensing resolution and long\u2010term structural and signal stability. Then, digital SERS nanoprobe immunoassays using AgNGS nanoprobes and magnetic nanoparticles conjugated with detection and capture antibodies for carbohydrate antigen 19\u20109 (CA19\u20109) and apolipoprotein A1 (APOA1) are developed for their quantitative detection in the clinical serum samples of pancreatic cancer (PC). Furthermore, digitization of the SERS intensity\u2010based assay outcomes into On\/Off states allows significant improvement in limits of detection and quantification for biomarker detection. Finally, the digital AgNGS nanoprobe immunoassay enables quantitative detection of both CA19\u20109 and APOA1 from the 150 clinical serum samples of PC patients, which are integrated with machine learning analysis via bootstrap sampling and logistic regression modeling for the diagnosis of early\u2010stage PC, achieving a high AUC of 0.988. AgNGS nanoprobe immunoassays offer an effective liquid biopsy route for profiling various blood biomarkers associated with many diseases.<\/jats:p>","DOI":"10.1002\/smtd.202600005","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T07:24:48Z","timestamp":1775633088000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Digital SERS Nanoprobe Immunoassay With Single\u2010Particle Sensing Resolution for Detection of Pancreatic Cancer Biomarkers From Clinical Blood Samples"],"prefix":"10.1002","volume":"10","author":[{"given":"Chanhee","family":"Choi","sequence":"first","affiliation":[{"name":"Department of Materials Science and Chemical Engineering Hanyang University  Ansan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Chemical Engineering Hanyang University  Ansan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sohyun","family":"Moon","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Chemical Engineering Hanyang University  Ansan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u2010Jun","family":"Hwang","sequence":"additional","affiliation":[{"name":"School of Chemistry and Biochemistry Georgia Institute of Technology  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong\u2010Yeon","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Chemical Engineering Hanyang University  Ansan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seokhyun","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Electronics &amp; Electrical Engineering, College of Engineering Dankook University  Yongin Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin\u2010Hyeok","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Bundang Hospital Seoul National University College of Medicine  Seongnam Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwangrok","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Bundang Hospital Seoul National University College of Medicine  Seongnam Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong\u2010Chan","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Bundang Hospital Seoul National University College of Medicine  Seongnam Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6256-7713","authenticated-orcid":false,"given":"Jong\u2010Ho","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Chemical Engineering Hanyang University  Ansan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-73525-y"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.22"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.13027"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i24.7864"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1067\/j.cpradiol.2020.08.002"},{"key":"e_1_2_8_7_1","first-page":"3684","article-title":"Pancreatic Cancer Detection and Characterization: State of the Art and Radiomics","volume":"25","author":"Granata V.","year":"2021","journal-title":"European Review for Medical and Pharmacological Sciences"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3348\/jksr.2023.0100"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-02021-w"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-024-03166-w"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2020.188409"},{"key":"e_1_2_8_12_1","first-page":"105","article-title":"The Clinical Utility of Serum CA 19\u20109 in the Diagnosis, Prognosis and Management of Pancreatic Adenocarcinoma: an Evidence Based Appraisal","volume":"3","author":"Ballehaninna U. 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