Direct SERS Detection of mRNA Cancer Biomarkers Using Spikey Nanorattle Biosensors
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.
