Ionic Liquid-Based Biosensors for Disease X: Research Trends, Platform Gaps, and Translational Challenges

The COVID-19 pandemic exposed profound vulnerabilities in global diagnostic infrastructures, highlighting the urgent need for rapid, sensitive, and field-deployable biosensors to manage future outbreaks (Disease X). Ionic liquids (ILs), characterized by their tunable solvation, high ionic conductivity, and exceptional thermal stability, are emerging as transformative materials in sensor engineering. This review critically evaluates the integration of ILs across diverse biosensor platforms, moving beyond their conventional roles to assess their specific utility in pandemic preparedness. We analyze global research trends, demonstrating the potential of IL-based pathogen detection. Furthermore, we explore how ILs facilitate not only the direct electrochemical and optical detection of primary pathogens but also the monitoring of pandemic-associated secondary health parameters, such as cytokine storms (e.g., IL-6), metabolic distress, and hematological or organ-level complications. By bridging the gap between sample preparation, such as rapid, cold-chain-free nucleic acid extraction, and ultra-sensitive signal transduction, IL-based platforms offer a promising route toward decentralized surveillance. We deliberately layer this evidence: mechanistic support for IL-mediated gains in electron transfer and bioreceptor stabilization is strong, analytical support for low detection limits in defined matrices is substantial, but deployment evidence remains limited, as most systems are still laboratory prototypes. Finally, we discuss current translational challenges, including biocompatibility and standardization, outlining a roadmap for deploying IL-integrated diagnostics in resource-limited settings.