Key Laboratory of Colloid and Interface Chemistry, Shandong University, Ministry of Education, Jinan 250100, China.
Qilu University of Technology (Shandong Academy of Sciences), Shandong Analysis and Test Center, Jinan 250014, China.
Anal Chem. 2020 Mar 3;92(5):3867-3873. doi: 10.1021/acs.analchem.9b05317. Epub 2020 Feb 18.
Multiplex detection of tumor markers in blood with high specificity and high sensitivity is critical to cancer diagnosis, treatment, and prognosis. Herein, we demonstrate a strategy for simultaneous detection of multiple tumor markers in blood by functional liquid crystal (LC) sensors assisted with target-induced dissociation (TID) of an aptamer for the first time. Magnetic beads (MBs) coated with an aptamer (apt1) are employed to specifically capture target proteins in blood. After incubation of the obtained protein-coated MBs with duplexes of another aptamer (apt2) and signal DNA, sandwich complexes of apt1/protein/apt2 are formed on the MBs due to specific recognition of target proteins by apt2, which induces release of signal DNA into the aqueous solution. Subsequently, signal DNA is specifically recognized by highly sensitive DNA-laden LC sensors. Using this strategy, a 3D printed optical cell was employed to enable simultaneous detection of multiple tumor markers such as carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), and prostate specific antigen (PSA) with high specificity and high sensitivity. Overall, this effective and low-cost multiplex approach takes advantage of the easy separation of MBs, high specificity of aptamer-based recognition, and high sensitivity of functional LC sensors. Plus, it offers a performance that is competitive to that of commercial ELISA kits without potential interference from hemolysis, which makes it very promising in multiplex detection of tumor markers in clinical applications.
高特异性和高灵敏度的血液肿瘤标志物多重检测对于癌症的诊断、治疗和预后至关重要。在此，我们首次展示了一种利用功能液晶（LC）传感器辅助适体靶标诱导解离（TID）进行血液中多种肿瘤标志物同时检测的策略。用适体（apt1）涂覆的磁性珠（MBs）用于特异性捕获血液中的靶蛋白。在获得的蛋白包被的 MBs 与另一个适体（apt2）和信号 DNA 的双链体孵育之后，由于 apt2 对靶蛋白的特异性识别，apt1/蛋白/apt2 的夹心复合物在 MBs 上形成，这导致信号 DNA 被释放到水溶液中。随后，信号 DNA 被高度敏感的载有 DNA 的 LC 传感器特异性识别。使用这种策略，通过 3D 打印的光学池可以同时检测多种肿瘤标志物，例如癌胚抗原（CEA）、甲胎蛋白（AFP）和前列腺特异性抗原（PSA），具有高特异性和高灵敏度。总的来说，这种有效且低成本的多重方法利用了 MBs 的易于分离、基于适体的识别的高特异性和功能 LC 传感器的高灵敏度。此外，它提供了与商业 ELISA 试剂盒相当的性能，而不会受到溶血的潜在干扰，这使其在临床应用中对肿瘤标志物的多重检测非常有前景。
