Titanium nitride meta-biosensors targeting extracellular vesicles for high-sensitivity prostate cancer detection

Disposable plasmonic metasurfaces with high biosensing performance are urgently sought for clinical label-free detection. Low-cost aluminum (Al) and titanium nitride (TiN) offer promising alternatives to noble metals for constructing these metasurfaces. However, Al suffers from limited chemical stability, and TiN exhibits weak plasmonic effects, both of which hinder their application in meta-biosensing. Here we integrate their complementary advantages and propose the TiN/Al meta-biosensors. They not only empower the unique near-field enhancement for sensing by TiN/Al hybrid plasmonic modes, but also construct a robust TiN armor against external wear, heat, moisture and corrosion during the bio-detection process. Compared to traditional gold-based counterparts, our meta-biosensors offer superior optical sensitivity at a much lower cost and with fewer pretreatment steps. The excellent biosensing performance facilitates the development of a high-throughput detection system for serum small extracellular vesicles (sEVs), aiding in the diagnosis and follow-up of prostate cancer. The sEVs meta-biosensing demonstrates a diagnostic sensitivity of 100% for significantly distinguishing early cancer, breaking through the conventional testing limitation. Moreover, it doubles the prediction accuracy of cancer recurrence risk following surgery. Our research highlights the potential for large-scale development of powerful meta-biosensors based on non-noble materials, opening up significant opportunities in cancer diagnosis and prognosis.