Overview of Molecularly Imprinted Polymer-Based Optical Biosensors for Protein Detection

Protein biomarkers play an indispensable role in the early diagnosis, prognosis assessment, therapeutic monitoring, and treatment evaluation of diseases. Optical biosensors have emerged as promising alternatives for protein detection due to their label-free, real-time, and highly sensitive characteristics. Molecularly imprinted polymers (MIPs), known as “plastic antibodies,” can provide chemically stable, low-cost, and tailorable recognition elements through the formation of target-complementary cavities in polymer matrices, making them highly attractive for integration with optical sensing platforms. In this work, we systematically summarize the advances in MIP-based optical biosensors for protein detection. The fundamental principles of biosensors and recognition elements are introduced, followed by a brief overview of the key components of imprinting technology, such as imprinting materials, functional monomers, cross-linking agents, polymerization mechanisms, template fixation strategies, and template removal conditions. Then, we comprehensively evaluate the integration of MIPs with various optical transduction techniques, including fluorescence, chemiluminescence, electrochemiluminescence, surface-enhanced Raman scattering, colorimetry, and surface plasmon resonance. Finally, the major challenges are discussed, and future development directions are proposed. This review aims to provide systematic theoretical references and useful insights for the rational design, performance improvement, and clinical translation of MIP-based optical biosensors for protein detection.