Spikey nanorattle–based SERS biosensors for direct detection of cancer-associated mRNA

Head and neck squamous cell carcinoma (HNSCC) remains one of the most common and lethal malignancies worldwide, originating mucosal epithelium of the oral cavity, pharynx, and larynx. [1]. Patient survival is strongly dependent on early diagnosis. In many low- and middle-resource settings, access to conventional molecular diagnostics remains limited due to the cost, complexity, and infrastructure requirements of conventional assays, underscoring the need for rapid, sensitive, and portable detection strategies [1]. Here, we present a plasmonics-enhanced biosensing platform based on spikey nanorattles (SpNR) that enables direct, amplification-free surface-enhanced Raman scattering (SERS) detection of cancer-associated mRNA biomarkers [2]. Our assay targets cytokeratin 14 (KRT14), an epithelial-specific mRNA that is overexpressed in HNSCC and has emerged as a promising diagnostic marker of malignant transformation. Detection is achieved using a magnetic bead–based sandwich hybridization scheme coupled with SpNR engineered in a core–gap–shell architecture to maximize electromagnetic field enhancement and Raman signals from target-bound probes. The resulting platform achieves a limit of detection of 90 femtomolar for KRT14 mRNA, demonstrating exceptional sensitivity without sample amplification [2]. In a pilot study involving clinical tissue samples, the biosensor reliably distinguished HNSCC-positive from HNSCC-negative specimens, underscoring its diagnostic specificity and translational relevance [2]. Collectively, these results demonstrate the feasibility of a highly sensitive, plasmonic assay for nucleic acid detection. By combining ultra sensitivity, simplicity, and portability, this approach offers a practical pathway toward point-of-care molecular diagnostics and highlights the broader potential of plasmonic nanostructures and SERS-based technologies for early cancer detection in resource-limited clinical environments.