SELEX-Based Aptamer Technologies for Toxin Analysis: Screening, Optimization, and Computational Assisted Design

The accurate and sensitive detection of toxin contamination remains a pressing challenge for food safety, environmental integrity, and public health, because conventional analytical methods suffer from high costs, poor field stability, and inadequate sensitivity for trace-level emerging contaminants. In this review, we provide a comprehensive overview of biosensor technologies for toxin detection, with a dedicated focus on nucleic acid aptamers and SELEX (Systematic Evolution of Ligands by Exponential Enrichment) technology. We systematically categorize nine SELEX variants developed for toxin detection, covering target-immobilized, library-immobilized, non-immobilized, cell-based, and high-throughput platforms, with an emphasis on their selection principles, applicability, and limitations. This review discusses computationally assisted aptamer discovery (e.g., AI-based sequence generation and molecular docking) as well as experimental post-SELEX optimization strategies such as cyclization, multivalent assembly, and structure-switching design. We then discuss key challenges and future perspectives, highlighting the shift from method-oriented to demand-oriented aptamer development through integrated SELEX strategies and AI-assisted design. Overall, this review covers mainstream SELEX technologies, aptamer selection, computational design, experimental optimization, and sensor integration to serve as a reference for next-generation toxin detection applications.