Polarization-Induced Multimode Terahertz Metamaterial for High-Sensitivity and Label-free Drug Monitoring

Abstract

Therapeutic drug monitoring (TDM) requires analytical technologies with high sensitivity, accuracy, and efficiency. Terahertz (THz) metamaterials offer strong THz electromagnetic field–analyte interactions and enable label-free detection with minimal sample consumption. However, most conventional designs rely on a single mode resonance (either single peak or multiple peaks), which limits modal diversity and thus causes in peak instability, sensitivity fluctuations, and a lack of real-time error validation. In this work, we propose a polarization-induced multimode THz metamaterial sensor that enable highly sensitive and accurate detection for TDM applications. By selectively exciting orthogonal electromagnetic modes under x- and y-polarized THz waves, the sensor generates multiple decoupled resonances with complementary field localization and well-separated spectral peaks. Each resonance mode couples to a distinct molecular vibration of the analyte, enabling multiplexed molecular identification and quantification. Clopidogrel sulfate, a widely used antithrombotic drug, was selected as a representative analyte validate the sensor performance. The resonance peaks of the polarization-induced multimode sensor were precisely adjusted to match the drug’s characteristic absorption bands. An ultralow limit of detection (LOD) of 3.0 pg/μL was achieved, representing a 1000-fold sensitivity improvement over conventional HPLC methods, while maintaining over 95% consistency. When applied to human blood samples, the sensor achieved 93.7% accuracy and a 5 min detection time per sample (postpretreatment), demonstrating its potential for rapid TDM. Overall, the polarization-induced multimode THz metamaterial offers a highly sensitive, accurate, and efficient platform for trace-level drug detection, providing a promising solution for personalized medication management.