Millions of people worldwide are negatively impacted by a diverse range of brain conditions known as neurodegenerative diseases. The work reports a GaN HEMT-based biosensing system for the early detection and monitoring of neurodegenerative disease biomarkers in clinically relevant concentration ranges. The developed system offers a high sensitivity of 19.40 µA/pg/ml, 0.52 mA/pg/ml, 0.69 mA/ng/ml, 0.13 mA/pg/ml, 23.66 µA/pg/ml, and 23.85 µA/pg/ml for the detection of UCH-L1, GFAP, S100B, IL-6, Aβ, and IFN-γ respectively. The proposed biofunctionalization assay has an excellent specificity and selectivity, signal-to-noise ratio of 1:16, 1:23, and 1:38 for UCH-L1, GFAP, and S100B detection respectively with a LoD of 0.06 fg/ml. The platform has good repeatability with an average sensitivity of 19.41 µA/pg/ml, 0.524 mA/pg/ml, and 0.704 mA/ng/ml for UCH-L1, GFAP, and S100B detection respectively. The sensors have a very good shelf-life for a storage time of 35 days with reductions of 1.39 %, 1.72 %, and 2.05 % in sensor response and 2.88 %, 2.76 %, and 2.96 % in sensitivity for UCH-L1, GFAP, and S100B respectively. The coefficient of variation (CV) values for conventional and meander-gated GaN HEMT biosensors were found to be ∼0.038 and ∼0.026 respectively. A slight variation of ∼4.41 % in sensor response when the sensor was reused clearly demonstrates the sensor’s reusability. A very high resolution with detection capability in the ultra-low concentration of fg/ml with good linearity and quantifiable sensor response which is a key requirement for early-stage detection of diseases has been observed for sensor design with source-to-drain distance () of 10 µm. Thus, the platform capability and suitability for early detection and prognosis of neurodegenerative disease detection and monitoring have been demonstrated. Further, the system can be imperative in patient screening in clinical, sports, and warfare for CT or MRI scan requirements.

Abstract

Psychiatric disorders pose a significant global health challenge, exacerbated by the COVID-19 pandemic and insufficiently addressed by the current treatments. This review explores the emerging role of bile acids and the TGR5 receptor in the pathophysiology of psychiatric conditions, emphasizing their signaling within the gut-brain axis. We detail the synthesis and systemic functions of bile acids, their transformation by gut microbiota, and their impact across various neuropsychiatric disorders, including major depressive disorder, general anxiety disorder, schizophrenia, autism spectrum disorder, and bipolar disorder. The review highlights how dysbiosis and altered bile acid metabolism contribute to the development and exacerbation of these neuropsychiatric disorders through mechanisms involving inflammation, oxidative stress, and neurotransmitter dysregulation. Importantly, we detail both pharmacological and non-pharmacological interventions that modulate TGR5 signaling, offering potential breakthroughs in treatment strategies. These include dietary adjustments to enhance beneficial bile acids production and the use of specific TGR5 agonists that have shown promise in preclinical and clinical settings for their regulatory effects on critical pathways such as cAMP-PKA, NRF2-mediated antioxidant responses, and neuroinflammation. By integrating findings from the dynamics of gut microbiota, bile acids metabolism, and TGR5 receptor related signaling events, this review underscores cutting-edge therapeutic approaches poised to revolutionize the management and treatment of psychiatric disorders.