High-sensitivity label-free terahertz metasurface sensor for REGγ detection in complex biofluids

Accurate detection of ultralow-abundance regulatory proteins in biofluids is essential for disease diagnosis and clinical analysis. REGγ (PA28γ/PSME3), an ATP-independent proteasome activator involved in protein degradation, cell-cycle regulation, and bone metabolism, remains challenging to quantify due to its low serum concentration and interference from complex biological matrices, which limit the sensitivity and reliability of conventional immunoassays. Here, we developed a label-free terahertz (THz) metasurface sensor with an HS-PEG-NHS-functionalized biointerface for high-sensitivity detection of REGγ. The engineered interface facilitates covalent antibody immobilization and provides a PEG-based functional interface for REGγ recognition, thereby supporting sensitive detection in complex biological samples. The sensor exhibits a sensitivity of 75 GHz RIU^-1 and shows a measurable response at the lowest tested REGγ concentration of 50 pg mL^-1 over a broad linear range. Furthermore, the platform demonstrates enabled detection of REGγ in clinical serum samples, with the lowest REGγ concentration measured among the analyzed clinical serum samples being 90.77 pg mL^-1 and showing distinguishable responses between the limited osteoporosis and healthy control samples examined in this preliminary study. This work provides a simple, reliable, and label-free THz biosensing strategy for sensitive detection of low-abundance protein biomarkers in complex biological samples.