Molecule-Specific Terahertz Biosensors Based on an Aptamer Hydrogel-Functionalized Metamaterial for Sensitive Assays in Aqueous Environments

Metamaterial-inspired terahertz (THz) biosensors are devoted to developing high-sensitivity and label-free biosensing strategies. However, most meaningful molecular signals are obscured by the strong THz absorption of solvent water. Most reported THz biosensors require the tested samples to be tediously dried or replaced with a low-absorption medium, which impairs the original bioactivity and the distribution homogeneity of targets. As described in this proposed strategy, a molecule-specific THz biosensor was fabricated from an aptamer hydrogel-functionalized THz metamaterial. Benefitting from the strong interaction with the localized electric field of the metamaterial, trace thrombin-induced variations in the hydration state of the hydrogel can be sensitively probed, which was investigated experimentally and theoretically. The optimized THz biosensor exhibited remarkable specificity for actual serum sample assays and excellent sensitivity, with a relatively low detection limit of 0.40 pM in the human serum matrix. The proposed strategy could serve as a model system to develop various molecule-specific THz biosensors for aqueous molecule sensing.