Cao Shengli, Xiao Gang, Liao Wenjin, Zhao Boxiang, Xie Shuqi, Liu Zhenguo, Chen Wei, Yue Zhao
Department of Microelectronics, Nankai University, Tianjin 300350, China.
Gaoqing People's Hospital, Zibo, Shandong 256399, China.
ACS Sens. 2025 Jul 25;10(7):5186-5198. doi: 10.1021/acssensors.5c01306. Epub 2025 Jun 28.
The emerging molecularly imprinted polymer (MIP) films, combined with various transducers, have drawn significant attention for biomarker detection. Currently, MIP films exhibit inferior performance and a limited detection variety range when detecting macromolecules because MIP films are unable to form effective cavities for macromolecule detection and their poor electrical and optical properties do not meet the requirements of transducers. To address these problems, MIP films were fabricated by dual-functional monomers (-phenylenediamine and pyrrole) in this work. MIP films were further integrated with a photoelectrochemical (PEC) transducer based on gold nanoclusters (AuNCs) to develop MIP-PEC sensors. Experimental results indicated that dual-functional monomers significantly enhanced the form of effective cavities with controllable number and orientation, electrical properties, and optical properties of the MIP film. Furthermore, the introduction of the MIP film onto AuNCs improved the stability of the MIP-PEC sensor and formed a heterojunction to enhance the photoelectric property of the sensor. Then, the sensing mechanism was elucidated with structural competitive binding, including size, shape, and binding sites, through cross-detection of PD-L1, CYFRA21-1, and cortisol with MIP-PEC sensors of varying cavity sizes. Finally, MIP-PEC sensors were expanded to a light-addressable MIP-PEC platform to detect PD-L1, CYFRA21-1, cortisol, and 4-methoxyphenylacetic acid in blood samples from patients with nonsmall cell lung cancer for early diagnosis and treatment evaluation. Therefore, the combination of dual-functional MIP films with PEC transducers represents a promising strategy for the high-sensitivity detection of molecules with various sizes, particularly for macromolecules. The light-addressable MIP-PEC platform provides a novel approach for the multichannel detection of multiple biomarkers.
新兴的分子印迹聚合物（MIP）薄膜与各种传感器相结合，在生物标志物检测方面引起了广泛关注。目前，MIP薄膜在检测大分子时表现出较差的性能和有限的检测种类范围，因为MIP薄膜无法形成用于大分子检测的有效空腔，并且其较差的电学和光学性能不符合传感器的要求。为了解决这些问题，本工作采用双功能单体（对苯二胺和吡咯）制备了MIP薄膜。MIP薄膜进一步与基于金纳米簇（AuNCs）的光电化学（PEC）传感器集成，以开发MIP-PEC传感器。实验结果表明，双功能单体显著增强了MIP薄膜有效空腔的形成，其数量和取向、电学性能以及光学性能均可控制。此外，将MIP薄膜引入AuNCs提高了MIP-PEC传感器的稳定性，并形成异质结以增强传感器的光电性能。然后，通过使用不同空腔尺寸的MIP-PEC传感器对PD-L1、CYFRA21-1和皮质醇进行交叉检测，从尺寸、形状和结合位点等方面阐明了结构竞争性结合的传感机制。最后，将MIP-PEC传感器扩展到光寻址MIP-PEC平台，用于检测非小细胞肺癌患者血样中的PD-L1、CYFRA21-1、皮质醇和4-甲氧基苯乙酸，以进行早期诊断和治疗评估。因此，双功能MIP薄膜与PEC传感器相结合是一种用于高灵敏度检测各种尺寸分子，特别是大分子的有前景的策略。光寻址MIP-PEC平台为多种生物标志物的多通道检测提供了一种新方法。
