{"title":"基于胆管聚集素的消化内镜与光纤生物传感器联合实时诊断胆管癌。","authors":"Long Gao, Baoquan Xiao, Yanyan Lin, Xidong Fang, Shun He, Mingzhen Bai, Lingen Zhang, Yanni Ma, Ningning Mi, Wenkang Fu, Chongfei Huang, Liang Tian, Jinyu Zhao, Ruyang Zhong, Zhen Liu, Yanxian Ren, Chao Zhang, Ruoshui Wang, Chenjun Tian, Hui Sun, Emmanuel Melloul, Qiangqiang Zhang, Jinqiu Yuan, Ping Yue, Liyun Ding, Wenbo Meng","doi":"10.1016/j.medj.2025.100843","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Early diagnosis of cholangiocarcinoma (CCA) remains challenging, but liquid biopsy is emerging as a promising detection strategy. Here, we identified a novel bile biomarker for CCA and developed an optic fiber biosensor integrated with digestive endoscopy for real-time diagnosis in vivo.</p><p><strong>Methods: </strong>A total of 583 subjects and two proteomic analyses were used to screen and validate biomarkers for CCA, and then the corresponding antibodies were generated to construct a surface plasmon resonance (SPR)-based optic fiber biosensor. The diagnostic performance of the biosensor was validated in 120 patients in vitro, and its biological characteristics were assessed under various physiological conditions. Finally, its real-time detection and biosafety in vivo were verified in pigs and patients.</p><p><strong>Findings: </strong>Clusterin (CLU) has been identified as a promising biomarker for CCA. Anti-CLU antibodies can specifically bind antigens with a K<sub>D</sub> value of 0.231 nM, and the diameter of the antibody-coated biosensor is only 0.488 mm. The optic fiber biosensor can accurately detect different concentrations of CLU with an R<sup>2</sup> value of 0.989, and it cannot be disturbed by other free proteins, ions, or different temperatures, pH levels, and colors. The biosensor can identify CCA within 2 s with an area under curve (AUC) of 0.854. Moreover, the biosensor can be easily introduced into porcine bile ducts via digestive endoscopy with excellent biocompatibility. Then, the biosensor was applied to three patients with non-calculous biliary strictures, and the results of real-time detection matched postoperative pathology.</p><p><strong>Conclusions: </strong>The CLU-based biosensor-endoscopy system enables accurate diagnosis of CCA through real-time in vivo detection, offering significant clinical translational potential.</p><p><strong>Funding: </strong>Funding information is shown in the acknowledgments.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100843"},"PeriodicalIF":11.8000,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Real-time diagnosis of cholangiocarcinoma by combining digestive endoscopy and optic fiber biosensors based on bile clusterin.\",\"authors\":\"Long Gao, Baoquan Xiao, Yanyan Lin, Xidong Fang, Shun He, Mingzhen Bai, Lingen Zhang, Yanni Ma, Ningning Mi, Wenkang Fu, Chongfei Huang, Liang Tian, Jinyu Zhao, Ruyang Zhong, Zhen Liu, Yanxian Ren, Chao Zhang, Ruoshui Wang, Chenjun Tian, Hui Sun, Emmanuel Melloul, Qiangqiang Zhang, Jinqiu Yuan, Ping Yue, Liyun Ding, Wenbo Meng\",\"doi\":\"10.1016/j.medj.2025.100843\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Early diagnosis of cholangiocarcinoma (CCA) remains challenging, but liquid biopsy is emerging as a promising detection strategy. Here, we identified a novel bile biomarker for CCA and developed an optic fiber biosensor integrated with digestive endoscopy for real-time diagnosis in vivo.</p><p><strong>Methods: </strong>A total of 583 subjects and two proteomic analyses were used to screen and validate biomarkers for CCA, and then the corresponding antibodies were generated to construct a surface plasmon resonance (SPR)-based optic fiber biosensor. The diagnostic performance of the biosensor was validated in 120 patients in vitro, and its biological characteristics were assessed under various physiological conditions. Finally, its real-time detection and biosafety in vivo were verified in pigs and patients.</p><p><strong>Findings: </strong>Clusterin (CLU) has been identified as a promising biomarker for CCA. Anti-CLU antibodies can specifically bind antigens with a K<sub>D</sub> value of 0.231 nM, and the diameter of the antibody-coated biosensor is only 0.488 mm. The optic fiber biosensor can accurately detect different concentrations of CLU with an R<sup>2</sup> value of 0.989, and it cannot be disturbed by other free proteins, ions, or different temperatures, pH levels, and colors. The biosensor can identify CCA within 2 s with an area under curve (AUC) of 0.854. Moreover, the biosensor can be easily introduced into porcine bile ducts via digestive endoscopy with excellent biocompatibility. Then, the biosensor was applied to three patients with non-calculous biliary strictures, and the results of real-time detection matched postoperative pathology.</p><p><strong>Conclusions: </strong>The CLU-based biosensor-endoscopy system enables accurate diagnosis of CCA through real-time in vivo detection, offering significant clinical translational potential.</p><p><strong>Funding: </strong>Funding information is shown in the acknowledgments.</p>\",\"PeriodicalId\":29964,\"journal\":{\"name\":\"Med\",\"volume\":\" \",\"pages\":\"100843\"},\"PeriodicalIF\":11.8000,\"publicationDate\":\"2025-09-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Med\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1016/j.medj.2025.100843\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Med","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.medj.2025.100843","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Real-time diagnosis of cholangiocarcinoma by combining digestive endoscopy and optic fiber biosensors based on bile clusterin.
Background: Early diagnosis of cholangiocarcinoma (CCA) remains challenging, but liquid biopsy is emerging as a promising detection strategy. Here, we identified a novel bile biomarker for CCA and developed an optic fiber biosensor integrated with digestive endoscopy for real-time diagnosis in vivo.
Methods: A total of 583 subjects and two proteomic analyses were used to screen and validate biomarkers for CCA, and then the corresponding antibodies were generated to construct a surface plasmon resonance (SPR)-based optic fiber biosensor. The diagnostic performance of the biosensor was validated in 120 patients in vitro, and its biological characteristics were assessed under various physiological conditions. Finally, its real-time detection and biosafety in vivo were verified in pigs and patients.
Findings: Clusterin (CLU) has been identified as a promising biomarker for CCA. Anti-CLU antibodies can specifically bind antigens with a KD value of 0.231 nM, and the diameter of the antibody-coated biosensor is only 0.488 mm. The optic fiber biosensor can accurately detect different concentrations of CLU with an R2 value of 0.989, and it cannot be disturbed by other free proteins, ions, or different temperatures, pH levels, and colors. The biosensor can identify CCA within 2 s with an area under curve (AUC) of 0.854. Moreover, the biosensor can be easily introduced into porcine bile ducts via digestive endoscopy with excellent biocompatibility. Then, the biosensor was applied to three patients with non-calculous biliary strictures, and the results of real-time detection matched postoperative pathology.
Conclusions: The CLU-based biosensor-endoscopy system enables accurate diagnosis of CCA through real-time in vivo detection, offering significant clinical translational potential.
Funding: Funding information is shown in the acknowledgments.
期刊介绍：
Med is a flagship medical journal published monthly by Cell Press, the global publisher of trusted and authoritative science journals including Cell, Cancer Cell, and Cell Reports Medicine. Our mission is to advance clinical research and practice by providing a communication forum for the publication of clinical trial results, innovative observations from longitudinal cohorts, and pioneering discoveries about disease mechanisms. The journal also encourages thought-leadership discussions among biomedical researchers, physicians, and other health scientists and stakeholders. Our goal is to improve health worldwide sustainably and ethically.
Med publishes rigorously vetted original research and cutting-edge review and perspective articles on critical health issues globally and regionally. Our research section covers clinical case reports, first-in-human studies, large-scale clinical trials, population-based studies, as well as translational research work with the potential to change the course of medical research and improve clinical practice.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
