Silicon nitride-based nanopores as adaptive interfaces in next-generation decentralized biosensors for cancer detection: Progress, challenges, and paths toward real-world use

Early cancer detection is imperative to increase survival rates; however, it remains largely unattainable in low- and middle-income countries due to the reliance on centralized laboratory infrastructure. In this review, we present a critical evaluation of recent advances in Si 3 N 4 nanopore platforms, demonstrating how their mechanical robustness, chemical inertness, and integration within semiconductor manufacturing make them ideally suited for point-of-care applications. Progress in scalable fabrication, surface functionalization with aptamers and antifouling layers, and integration with microfluidic and portable electronic systems is detailed. However, considerable technical hurdles regarding biofouling, electrical noise in clinical matrices, batch-to-batch reproducibility, and clinical regulatory approval need to be addressed. Novel approaches, such as signal analysis using machine learning, hybrid sensing, and sustainable fabrication, may represent interesting possibilities that may help overcome these technical difficulties. Despite its suitability for widespread cancer detection using Si 3 N 4 nanopore technology, dedicated efforts have been devoted to mitigating all current challenges and unlocking its true capabilities.