Rapid Multianalyte Quantification of Brain Chemistry Using Si-Nanoribbon Bio-Field-Effect Transistor Sensors

Continuous real-time monitoring of chemical biomarkers is essential for advancing our understanding of neurological disorders and facilitating targeted therapeutic interventions. Conditions such as epilepsy involve disturbances in the excitatory-inhibitory balance of neural circuits, which are modulated by critical chemicals, including gamma-aminobutyric acid (GABA), lactate, and glutamate. While semiconductor field-effect transistor (FET)-based sensors are an exciting development in this area, significant limitations remain, including inadequate real-time detection capabilities and inconsistent surface functionalization. To address these shortcomings, we present a complementary metal-oxide-semiconductor (CMOS)-based FET nanowire device ("nanoribbon") for rapid and real-time biosensing of GABA, lactate, and glutamate. The sensor surface was functionally engineered to support selective and simultaneous detection of these neurochemicals in both buffered solutions and complex biological matrices such as artificial cerebrospinal fluid (aCSF). Aptamer bioreceptors were employed for lactate and glutamate, while monoclonal antibodies were used for GABA, facilitating highly selective, label-free detection. The nanosensing platform provides rapid and accurate chemical quantification within 10 min, achieving limits of detection (LOD) of 80 fM for GABA, 58 fM for glutamate, and 182 fM for lactate. This technology supports continuous neurochemical monitoring and holds strong potential to improve diagnostic accuracy and therapeutic efficacy in neurological care.