Highly Sensitive Detection and Discrimination of Cell Suspension Based on a Metamaterials-Based Biosensor Chip

Metamaterials (MMs)-based terahertz (THz) biosensors hold promise for clinical diagnosis, featuring label-free operation, simple, rapid detection, low cost, and multi-cell-type discrimination. However, liquid around cells causes severe interference to sensitive detection. Most existing MMs-based cell biosensors detect dead cells without culture medium (losing original morphology), hindering stable, sensitive multi-cell discrimination. Here, a terahertz biosensor composed of a microcavity and MMs can be used to detect and discriminate multiple cell types within suspension. Its detection mechanism relies on cellular size (radius)/density in suspension, which induces effective permittivity (<i>ε</i>_eff) differences. By designing MMs' split rings with luxuriant gaps, the biosensor achieves a theoretical sensitivity of ~328 GHz/RIU, enabling sensitive responses to suspended cells. It shows a robust, increasing frequency shift (610-660 GHz) over 72 h of cell apoptosis. Moreover, it discriminates nerve cells, glioblastoma (GBM) cells, and their 1:1 mixture with obviously distinct frequency responses (~650, ~630, ~620 GHz), which suggests effective and reliable multi-cell-type recognition. Overall, this study and its measurement method should pave the way for metamaterial-based terahertz biosensors for living cell detection and discrimination, and this technology may inspire further innovations in tumor investigation and treatment.