Enhanced Terahertz Specific Sensing for Alzheimer’s Marker by Metasurface-Analyte Union Modification on Microfluidic Sensor

Metasurface (MS)-based terahertz (THz) biosensors have attracted significant attention in the biological field due to their nondestructive and harmless interaction with biochemical samples. However, it is still challenging for specific detection in mixed samples via THz metasensors. In this work, we modified THz MS chips and target biomolecules, respectively, utilized immune binding and gold nanorods (GNRs), and achieved THz high-sensitive specific detection for Alzheimer's marker $\text{A}\beta _{\text {1-42}}$ protein via a microfluidic platform. A double-ring coupled metallic MS that can provide a strong localized field enhancement was fabricated and then modified with $\text{A}\beta _{\text {1-42}}$ -antibody by covalent binding to capture $\text{A}\beta _{\text {1-42}}$ . Moreover, GNRs were introduced to bind $\text{A}\beta _{\text {1-42}}$ , and the sensor's response to $\text{A}\beta _{\text {1-42}}$ is greatly enhanced. Through this sensor-analytes modification, the sensitivity of the sensor can reach 240.91 GHz $\cdot $ mL/nmol, and the limit of detection (LoD) is one order of magnitude higher than that without GNRs. In addition, the LoD for $\text{A}\beta _{\text {1-42}}$ reached 0.2 pmol/mL (1 ng/mL), which is 100 times higher than other nonspecific proteins. More importantly, the biosensor can also recognize $\text{A}\beta _{\text {1-42}}$ in a mixed sample with physiological limiting concentration. Our high selectivity and sensitivity nanomaterial-MS hybrid-based THz biosensor would give access to rich applications in label-free biosensing.