Abstract：
Circulating tumor cells (CTCs) are promising liquid biopsy biomarkers for early cancer detection and anti-cancer therapy evaluation. The ultra-low abundance of CTCs in blood samples requires highly sensitive and accurate detection ways. In this study, we propose the design of a dual-recognition electrochemical biosensor to improve both the specificity and signal response. PdPtCuRu mesoporous nanospheres (PdPtCuRu MNSs) with excellent three dimensions (3D) nanopore structures were synthesized by one-pot method and connected to mucin 1 (MUC1) aptamer to serve as signal amplification probe. Besides, superconductive carbon black, Ketjen Black (KB), and gold nanoparticles (AuNPs) modified organometallic frame (CeMOF-Au) were combined to work as signal transducer. The characteristic branching structure of KB provides abundant contact points to load CeMOF-Au to heighten the interface electron transfer rate. In addition, AuNPs were reduced on the surface of CeMOF, which could effectively bind the capture antibody and further enhance the conductivity. Under the optimized condition, the limit of detection (LOD) of the as-constructed biosensor was less than 10 cells mL-1 for model A549 cells, and showed good specificity and accuracy in spiked serum samples. We envision the as-proposed electrochemical biosensor would alternate as a useful tool for the clinical detection of CTCs for cancer diagnosis.
摘要：
循环肿瘤细胞（CTC）是用于早期癌症检测和抗癌治疗评估的有前途的液体活检生物标志物。血液样本中CTC的超低丰度需要高灵敏度和准确的检测方法。在这项研究中,我们提出了一种双识别电化学生物传感器的设计，以提高特异性和信号响应。通过一锅法合成了具有优异三维（3D）纳米孔结构的PdPtCuRu介孔纳米球（PdPtCuRuMNSs），并连接到粘蛋白1（MUC1）适体作为信号放大探针。此外,超导炭黑，KetjenBlack(KB),和金纳米粒子（AuNP）修饰的有机金属框架（CeMOF-Au）结合起来作为信号换能器。KB的特征性分支结构为负载CeMOF-Au提供了丰富的接触点，以提高界面电子转移速率。此外,AuNPs在CeMOF表面被还原,能有效结合捕获抗体,进一步提高导电性。在优化条件下,构建的生物传感器的检测限（LOD）对于A549模型细胞小于10细胞mL-1，并在加标血清样品中显示出良好的特异性和准确性。我们设想所提出的电化学生物传感器将替代作为用于癌症诊断的CTC的临床检测的有用工具。
