Fluorescence-based MOF biosensors toward simultaneous detection of COVID-19 and influenza: Design strategies and future prospects

• Metal-organic frameworks (MOFs) enable dual detection of COVID-19 and influenza. • Fluorescence-based MOF biosensors offer high sensitivity and multiplexing potential. • Integration with microfluidics and AI enhances real-time diagnostic performance. • Key challenges include MOF reproducibility, biocompatibility, and regulatory barriers. • MOF platforms show strong potential for point-of-care and smartphone-based diagnostics. • Proactively addressing all ethical and legal dimensions is essential for the responsible deployment of MOF-based biosensors. The concurrent threat of COVID-19 and influenza highlights the urgent need for rapid, accurate, and simultaneous diagnostic tools. Traditional techniques, such as PCR and ELISA, are limited by high costs, long turnaround times, and reliance on specialized laboratories. Metal-organic frameworks (MOFs) have demonstrated great potential as materials for viral biosensing due to their high porosity, tunability, and surface functionality, which enable multiple detection modalities, including fluorescence, electrochemical, and colorimetric sensing. This review explores the design strategies, detection mechanisms, and recent advances in MOF-based biosensors, with a focus on design strategies and sensing principles relevant to the simultaneous detection of COVID-19 and influenza. While true MOF-based fluorescence platforms enabling simultaneous differentiation of COVID-19 and influenza remain limited, this review consolidates transferable design principles from multi-virus systems to inform future diagnostics. It discusses the potential of functionalized MOFs for simultaneous virus recognition, highlights the integration of MOFs with microfluidic and wearable platforms, and emphasizes the role of artificial intelligence (AI), machine learning (ML), and smartphones in enhancing detection performance and scalability, as well as the ethical and legal considerations associated with the widespread use of biosensors. By consolidating recent findings, this review outlines key challenges, such as stability, reproducibility, and regulatory barriers, while proposing pathways for translating MOF-based simultaneous detection systems into clinically viable diagnostic tools.