化学
丰度(生态学)
液体活检
胰腺癌
分子
癌症
内科学
有机化学
医学
渔业
生物
作者
Xinjian Wang,Yongsheng Che,Songlin Liu,Bochen Ma,Yijun Liu,Jiao Lei,Yuan Liang,Yuxun Zhou,Jieer Ying,Yimin Zhang,Tian Chen,Tao Zhu,Lubin Qi,Yifei Jiang,Xiaohong Fang
标识
DOI:10.1021/acs.analchem.4c07031
摘要
Simultaneous analysis of multiple biomarkers can typically improve the sensitivity and specificity of a disease diagnosis. Low-abundance serum proteins have recently emerged as a novel class of biomarkers for diseases. Due to the low concentration, the low-abundance protein analysis relies on single-molecule immunoassay, which has a very limited dynamic range. As a result, simultaneous analysis of low- and high-abundance protein markers requires multiple instruments, which demands larger sample volumes and is cost-/labor-consuming. To overcome these limitations, we developed a single-molecule imaging technique that can detect low- and high-abundance protein markers simultaneously in one chip. By employing a hybrid biomarker capture strategy that involves both glass surface and bead immobilization, our method greatly extended the detection range of the single-molecule assay. We used the method for pancreatic cancer diagnosis and analyzed three serum biomarkers of different abundances, including LIF, CA19-9, and CA125. Combined analysis of the three biomarkers yielded exceptional sensitivity and specificity (AUC = 0.996), which is better than using any of the markers alone, including CA19-9 that is used in clinical practice (AUC = 0.804). Overall, we demonstrated a simple and cost-effective method that greatly extended the dynamic range of single-molecule imaging while maintaining the sensitivity, which has great potential in various clinical applications.
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