人附睾蛋白 4 (HE4) 是卵巢癌的诊断生物标志物，对于监测疾病的早期阶段至关重要。因此，开发简单、廉价且用户友好的生物传感器来进行灵敏和定量的 HE4 检测非常重要。在此，制备了一种基于普鲁士蓝（PB）作为信号指示剂和功能化金属有机框架纳米复合材料作为高效信号放大器的新型夹心型电化学免疫传感器，用于HE4的定量分析。原则上，科琴黑（KB）和TiMOF修饰的AuNPs（TiMOF-KB@AuNPs）可以加速电极表面的电子转移，并通过交联作为固定抗体的基质，从而提高测定灵敏度。与标记抗体共价结合的 PB 赋予生物传感器强烈的电化学信号。此外，通过监测PB的电活性可以间接检测HE4的浓度。受益于 PB 和 MOF 纳米复合材料的高信号放大能力，该策略表现出较宽的线性范围 (0.1-80 ng mL-1) 和较低的检测限 (0.02 ng mL-1)。因此，这项研究展示了在临床卵巢癌诊断和治疗中的巨大应用前景，并为检测其他癌症生物标志物提供了新的平台。版权所有 © 2024 Elsevier B.V. 保留所有权利。

Human epididymis protein 4 (HE4), a diagnostic biomarker of ovarian cancer, is crucial for monitoring the early stage of the disease. Hence, it is highly important to develop simple, inexpensive, and user-friendly biosensors for sensitive and quantitative HE4 assays. Herein, a new sandwich-type electrochemical immunosensor based on Prussian blue (PB) as a signal indicator and functionalized metal-organic framework nanocompositesas efficient signal amplifiers was fabricated for quantitative analysis of HE4. In principle, ketjen black (KB) and AuNPs modified on TiMOF (TiMOF-KB@AuNPs) could accelerate electron transfer on the electrode surface and act as a matrix for the immobilization of antibodies via cross-linking to improve the determination sensitivity. The PB that covalently binds to labeled antibodies endows the biosensors with intense electrochemical signals. Furthermore, the concentration of HE4 could be indirectly detected by monitoring the electroactivity of PB. Benefiting from the high signal amplification ability of the PB and MOF nanocomposites, this strategy displayed a wide linear range (0.1-80 ng mL-1) and a lower detection limit (0.02 ng mL-1). Hence, this study demonstrated great promise for application in clinical ovarian cancer diagnosis and treatment, and provided a new platform for detecting other cancer biomarkers.Copyright © 2024 Elsevier B.V. All rights reserved.