Integrated Single-Step Terahertz Metasensing for Simultaneous Detection Based on Exosomal Membrane Proteins Enables...

Exosomes (Exos) are emerging as noninvasive biomarkers for diagnosis and progression monitoring of gastric cancer (GC). However, the heterogeneity discrimination and ultrasensitive quantification of Exos presents a considerable analytical challenge, thereby impeding severely their clinical application. Herein, we propose an integrated terahertz metasensing platform for the discrimination of Exos in distinct subtypes of GC in a single step-through the simultaneous evaluation of the category and richness level of Exos membrane proteins. Characterized by dual-sided independent sensing capabilities with enhanced sensitivity (169 and 325 GHz per refractive index unit, respectively), the metasensor functionalized with antibodies simultaneously reflects the content of 2 membrane proteins in the terahertz spectral response. Our approach concurrently completes accurate differentiation and precise quantification of GC-subtype Exos by integrating dual-sided sensing information in merely a single assay. The dual-sided sensing design enhances the reliability of detection results. Moreover, combined with the signal amplification of gold nanoparticles, the platform experimentally demonstrates a superior dynamic response to Exos concentrations spanning from 1 × 10⁴ to 1 × 10⁸ particles/ml, with the limit of detection being 1 × 10⁴ particles/ml. This work provides new insights into multisensing metasurface design and paves the way for precise and personalized cancer treatment through the specific sensing of Exos.