Advanced Strategies and Mechanisms of Nanomaterial–Molecularly Imprinted Polymer Synergistically Functionalized Biosensors for Biomarker Detection

Biomarker detection demands low cost, rapid turnaround, interference resistance, and wide dynamic range. However, traditional immunoassays and nucleic acid amplification methods remain constrained by complex matrices, batch stability, and portability limitations. Molecularly imprinted polymers (MIPs) exhibit “artificial antibody”-like specific recognition and high stability, while nanomaterials (NMs), depending on their composition, structure, and interfacial organization, can provide conductive pathways, catalytic activity, high-density loading sites, or mass-transfer-favorable architectures. Electrochemical biosensors synergistically constructed from these two components achieve complementary functions in recognition, mass transfer, and signal transduction. This paper systematically reviews key strategies and mechanisms for NM–MIP synergistic construction, focusing on six synergistic strategies that target key bottlenecks in mass transfer, signal generation, and interfacial stability: dynamic response regulation, hierarchical structural engineering, anti-fouling interfaces, multi-signal cross-validation, catalytic–recognition integration, and interfacial binding regulation. Representative biomarker cases are analyzed to illustrate how functional modules can coordinate across sample processing, signal generation, and recognition confirmation to improve analytical reliability and overall sensing performance. Finally, the review discusses challenges in clinical translation, including consistent manufacturing, matrix interference, long-term stability, and standardized validation, while outlining future directions toward mechanism-guided imprint design, intelligent data-assisted optimization, and integration with microfluidic and wearable platforms for multiplexed biomarker detection.