Intelligent Molecular Logic Computing Toolkits: Nucleic Acid-Based Construction, Functionality, and Enhanced Biosensing Applications

Molecular logic computing is revolutionizing biosensing by enabling intelligent, programmable detection, moving beyond simple target recognition to advanced molecular-level information processing. By employing biological molecules such as DNA/RNA, proteins/enzymes, or even whole biological cells as building blocks for creating molecular logic toolkits, logic operations have made rapid progress in molecular logic-based biosensing. In this review, we present a comprehensive overview of intelligent molecular logic operation toolkits and their contributions to advancing biosensing technologies. We first outline the design principles of these toolkits, detailing various types of logic gates, including Boolean, combinatorial, and sequential logic, as well as advanced feedback systems, fuzzy logic, and reversible logic. We delve into the construction of DNA-based, synthetic, and nanomaterial-based logical operation toolkits. Following this, we explore the functionalities of intelligent molecular logic computing toolkits, which encompass modular multi-signal integration, activatable Lock-Key (OFF-ON) reconfigurable control, programmable control, and logic-gated nanomachines. We also elaborate on the analytical mechanisms underpinning molecular logic-gated operations that utilize various detection platforms, including fluorescent, colorimetric, and electrochemical techniques, along with artificial intelligence-powered and smartphone-based detection platforms. Applications spanning genetic analysis, cancer analysis, pathogen identification, living cell logic analysis, and point-of-care diagnostics are highlighted. Finally, the future challenges associated with molecular logic toolkits in enhancing biosensing and potential solutions were outlined, providing insights into practical obstacles as well as future trends and prospects.