Terahertz multiband metamaterial biosensor for ultrasensitive detection of PC-12 adrenal gland carcinoma cells through microenvironmental analysis

Adrenal gland cancer, particularly adrenocortical carcinoma (ACC), is an aggressive malignancy arising from the adrenal cortex’s secretory cells. ACC is often diagnosed at advanced, metastatic stages, necessitating surgical resection. However, its high recurrence rate and late-stage detection frequently require systemic therapies, which are generally ineffective, leading to poor survival outcomes. Early detection is, therefore, crucial for improving treatment efficacy. Identifying PC-12 adrenal gland carcinoma cells is essential for understanding neuroendocrine tumor progression and developing effective therapeutic strategies. This study presents a novel metamaterial (MTM)-based biosensor for detecting PC-12 carcinoma cells with exceptional sensitivity. The sensor features three resonators fabricated on 0.2-μm-thick aluminum (Al) layers embedded within a 10-μm-thick polyethylene terephthalate (PET) substrate. The sensor is highly compact with an overall dimension of just 150 × 150 μm², making it well-suited for integration into portable diagnostic systems. Operating in the terahertz frequency range (0.5 THz to 5.0 THz), the device achieves remarkable performance, with an absorption rate exceeding 99% across eight operating bands and surpassing 99.9% in two bands. Additionally, it boasts high quality factor (approaching 30) and an exceptional sensitivity of nearly 4,000,000 THz/RIU. The sensor’s outstanding performance is attributed to meticulous geometric tuning and architectural optimization, significantly enhancing its sensitivity for cancer detection. Numerical validation was conducted using full-wave electromagnetic simulations, including electric and magnetic field distribution analysis, surface current mapping, and scattering parameter evaluation. Comparative assessments against state-of-the-art biosensors demonstrated the proposed sensor’s superiority in key performance metrics such as quality factor, figure of merit (FOM), and absorption efficiency. The sensor’s efficacy in detecting PC-12 adrenal carcinoma cells was verified by integrating it into a Microwave Imaging (MWI) system. The device successfully distinguished between healthy and cancerous cells by capturing distinct electromagnetic signatures through electric (E) and magnetic (H) field variations. These results underscore the sensor’s potential as a highly sensitive, non-invasive diagnostic tool for early-stage detection of adrenal gland cancer and other malignancies. • The proposed biosensor exhibits superior sensitivity (3906000 THz/RIU), high figure of merit (181168831 RIU⁻¹), and a quality factor of 28.279, significantly outperforming conventional biosensors. The high sensitivity ensures precise detection of small biomolecular changes, making it highly effective for early cancer diagnostics. • Table 2 , , Table 4 , Table 5 illustrate key performance metrics, demonstrating that the proposed biosensor surpasses prior designs in terms of absorption efficiency, operational bandwidth, and biomolecular detection sensitivity. Compared to previously developed THz biosensors, the proposed design offers a broader frequency range, improved selectivity, and higher absorption efficiency. • The biosensor's ultra-compact PET-based structure and aluminum resonator layer provide enhanced absorption across multiple THz peaks, ensuring high diagnostic accuracy. The choice of materials contributes to reduced fabrication costs while maintaining excellent mechanical stability and electrical performance. • The biosensor operates efficiently over a wide THz spectrum (0.5–5 THz), allowing for multi-frequency analysis of biomolecular interactions. This capability makes it suitable for diverse biosensing applications, including cancer detection, virus identification, and protein analysis. • Due to its excellent biocompatibility, non-invasive nature, and adaptability to real-time monitoring, this biosensor is a strong candidate for integration into clinical oncology diagnostics. The ability to detect PC-12 adrenal gland carcinoma cells with high precision positions this sensor as a potential alternative to traditional biopsy-based diagnostic methods. • The sensor’s simple three-layer aluminum-PET-aluminum structure enables cost-effective mass production. The manufacturing process can be adapted for large-scale fabrication using existing microfabrication techniques, making it feasible for commercial biomedical applications. • Unlike many traditional biosensors that target a single biomarker, the proposed THz biosensor's multiband absorption capabilities allow for multiplexed sensing. This feature enhances its usability in detecting multiple cancer types or differentiating between various disease stages, improving diagnostic efficiency. • The biosensor's performance could be further enhanced through the incorporation of advanced nanomaterials, such as graphene or quantum dots, to improve its sensitivity and selectivity. Additionally, integration with AI-based spectral analysis could further refine its diagnostic accuracy, making it an indispensable tool in modern medical diagnostics.