Dual-Functional Monomer-Based Molecularly Imprinted Light-Addressable Photoelectrochemical Platform for Multichannel Detection of Molecules with Various Sizes

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 (<i>o</i>-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.