Molecularly Imprinted Polymer Sensor Empowered by Bound States in the Continuum for Selective Trace-Detection of TGF-beta

The integration of advanced materials and photonic nanostructures can lead to enhanced biodetection capabilities, crucial in clinical scenarios and point-of-care diagnostics, where simplified strategies are essential. Herein, a molecularly imprinted polymer (MIP) photonic nanostructure is demonstrated, which selectively binding to transforming growth factor-beta (TGF-beta), in which the sensing transduction is enhanced by bound states in the continuum (BICs). The MIP operating as a synthetic antibody matrix and coupled with BIC resonance, enhances the optical response to TGF-beta at imprinted sites, leading to an augmented detection capability, thoroughly evaluated through spectral shift and optical lever analogue readout. The validation underscores the MIP-BIC sensor capability to detect TGF-beta in spiked saliva, achieving a limit of detection of 10 fM and a resolution of 0.5 pM at physiological concentrations, with a precision of two orders of magnitude above discrimination threshold in patients. The MIP tailored selectivity is highlighted by an imprinting factor of 52, showcasing the sensor resistance to interference from other analytes. The MIP-BIC sensor architecture streamlines the detection process eliminating the need for complex sandwich immunoassays and demonstrates the potential for high-precision quantification. This positions the system as a robust tool for biomarker detection, especially in real-world diagnostic scenarios. Combining molecular imprinting polymers and refractometric optical sensing based on bound states in the continuum allows demonstrating a new platform for ultra-sensitive biodetection, which is capable of large selectivity and specificity necessary in clinical scenarios. The device is applied for detecting TGF-beta cytokine in saliva outperforming state-of-the-art technologies. image