Advanced nano-biosensors with multiscale applications: A comprehensive review

Nanobiosensors have emerged as transformative analytical platforms by integrating nanoscale materials with biological recognition to achieve ultrasensitive, selective, and real-time detection across diverse application domains. This comprehensive review critically synthesizes recent advances in nanobiosensor design through a unified multiscale framework that links nanoscale sensing mechanisms, mesoscopic device architectures, and macroscopic system integration. We systematically evaluate major nanomaterials, including carbon nanotubes, quantum dots, metallic nanoparticles, nanowires, and polymer nanocomposites, correlating their physicochemical properties with sensing performance metrics such as sensitivity, selectivity, stability, and reproducibility. Emphasis is placed on mechanistic signal transduction pathways, including electron transfer, field-effect modulation, plasmonic resonance, and fluorescence-based energy transfer, to explain observed performance trade-offs. Multiscale application pathways are analyzed across healthcare diagnostics, environmental monitoring, food safety, and agriculture, demonstrating that practical deployment depends on coordinated integration beyond nanoscale sensitivity alone. Key challenges limiting translation, including biocompatibility, fouling, fabrication scalability, and long-term signal stability, are critically assessed alongside emerging mitigation strategies such as hybrid architectures, surface engineering, and AI-assisted signal processing. By reframing multiscale nanobiosensing as a system-level design paradigm rather than a material-centric pursuit, this review provides actionable guidelines for rational sensor development and highlights future directions toward robust, scalable, and application-ready nanobiosensor technologies for global deployment.