Integrating AI with Biosensors and Voltammetry for Neurotransmitter Detection and Quantification: A Systematic Review

Background: The accurate and timely diagnosis of neurodegenerative disorders such as Parkinson’s disease, Alzheimer’s disease, and major depressive disorder critically depends on real-time monitoring and precise interpretation of authentic neurotransmitter (NT) signal dynamics in complex biological fluids (CBFs), including cerebrospinal fluid. These NT dynamics are governed by both the type and concentration of NTs present in the CBFs. However, current biosensors face significant limitations in sensitivity and selectivity, thereby hindering reliable estimation (detection and quantification) of NTs. Though nanomaterials and bioenzymes have been utilized to modify sensor interfaces for enhanced performance, issues like signal convolution, electrode fouling, and inter-NT crosstalk persist. Objectives: This review aims to evaluate and synthesize current research on the use of artificial intelligence (AI), particularly machine learning (ML), pattern recognition (PR), and deep learning (DL), to improve the automated detection and quantification of neurotransmitters from complex biological fluids. Design: A systematic review of 33 peer-reviewed studies was conducted, focusing on the integration of AI methods in neurotransmitter estimation. The review includes an analysis of commonly studied NTs, the methodologies for their detection, data acquisition techniques, and the AI algorithms applied for signal processing and interpretation. Results: The studies reviewed demonstrate that AI-based approaches have shown considerable potential in overcoming traditional biosensor limitations by effectively deconvoluting complex, multiplexed NT signals. These techniques allow for more accurate NT estimation in real-time monitoring scenarios. The review categorizes AI methodologies by their application and performance in NT signal analysis. Conclusions: AI-enhanced NT monitoring represents a promising direction for advancing diagnostic and therapeutic capabilities in neurodegenerative diseases. Despite current challenges, such as sensor stability and NT interaction complexity, AI integration, particularly in applications like closed-loop deep brain stimulation (CLDBS), offers significant potential for more effective and personalized treatments.