Abstract
There is an urgent need to develop label-free, accurate detection techniques for gliomas due to the high aggressiveness and heterogeneity of glioma tissues. In this study, a polarization-insensitive terahertz metamaterial biosensor based on a quadruple rotationally symmetric superunit is proposed to address the issues of insufficient sensitivity and polarization-dependent interference associated with conventional metamaterials in terahertz spectroscopy. The structural parameters were optimized through theoretical modeling and electromagnetic simulations, leading to the design of C4-symmetric metamaterials with stable responses over a wide incidence angle range. These metamaterials effectively mitigate signal distortion caused by the random orientation of metamaterial placement during experiments. The experiments were conducted using a terahertz frequency-domain spectroscopy system (THz-FDS) to detect isolated glioma tissues. The results demonstrate that the sensor maintains polarization insensitivity across the full 0-360° range, significantly enhancing the contrast in dielectric properties between tumor and normal tissues. Furthermore, its resonance frequency shift exhibits a strong correlation with tissue thickness, increasing up to 26 µm, after which it stabilizes and no longer exhibits significant changes. This study confirms that polarization-insensitive metamaterials can overcome existing imaging limitations, reduce operator-induced human errors, and provide a novel, non-invasive detection solution for intraoperative boundary delineation and pathological diagnosis of gliomas, with strong potential for clinical translation.