Advancements in Nanomaterial-Based Biosensors for Neuropsychiatric and Neurodegenerative Diagnostics: From Biomarker Discovery to Clinical Translation.

Nanobiosensors, with their unique physicochemical properties, are transformative tools for diagnosing and monitoring neurodegenerative diseases and mental disorders. This article systematically reviews the latest progress of nanomaterial systems and integrated sensing modalities in neurological disease diagnosis. First, we clarify the multiple functional roles of nanomaterials in biosensors, including signal amplification, interface optimization, and spatial positioning, and compare the applicable scenarios of various sensing principles based on different nanomaterials. Second, we evaluate the design and integration strategies of molecular recognition elements (antibodies, nucleic acid aptamers, molecularly imprinted polymers, and CRISPR-Cas systems) and discuss their synergistic integration mechanisms for improving detection performance. In terms of detection targets, we focus on three applications: high-sensitivity quantification of established protein biomarkers, real-time monitoring of dynamic neurochemicals (dopamine, serotonin, glutamate), and emerging liquid biopsy targets such as exosomal cargo and circulating microRNAs. Finally, to address the core challenges of biofouling, sensitivity-selectivity trade-offs, and multiplex detection in complex matrices, we propose three breakthrough directions for next-generation diagnostics: deep integration of multimodal and multiplexing platforms, closed-loop chemical brain-computer interfaces (cBCIs), and AI-driven predictive diagnostic models, collectively enabling a transition from passive detection to active sensing and intervention for precise, rapid, and non-invasive neurological disease management.