Synergistic Dual-Nanoprobe Terahertz Metasurface Biosensor for Ultrasensitive Detection of Neuron-Specific Enolase

Direct detection of biomolecules using terahertz (THz) waves remains challenging due to their inherently weak signal responses. While metasurface-enhanced interactions offer a common solution, achieving scalable, nondestructive, and controllable molecular capture remains a key challenge. To address this challenge, we designed two complementary nanoprobes, AuNPs and Au@Fe3O4, for incorporation into a THz metasurface-based sensing platform. AuNPs efficiently enrich target molecules in high-field resonance regions for signal amplification. Au@Fe3O4 probes enable magnetic targeting and spatial localization under an external field. Using neuron-specific enolase (NSE), a key neuroendocrine biomarker, as the target analyte, our platform demonstrated strong linear detection from 0.01 to 50 ng/mL. It achieved ultralow limits of detection (LODs) of 0.007 ng/mL (AuNPs) and 0.003 ng/mL (Au@Fe3O4)─among the lowest reported for NSE via THz sensing. Significantly, the dual-probe strategy achieved synergistic enhancement. This synergistic dual-probe platform provides a promising strategy for highly sensitive and spatially controllable THz biosensing, facilitating high-precision, scalable biomarker detection in clinical diagnostics and point-of-care personalized medicine.