Aptamer-based biosensing strategies for influenza virus detection: a systematic and critical review of electrochemical and optical platforms.

Influenza virus remains a major global health challenge due to its genetic variability and frequent emergence of novel strains. Subtyping is determined by the diverse arrangements of hemagglutinin (HA) and neuraminidase (NA) glycoproteins, with HA frequently serving as the molecular target for diagnostic assays. Conventional detection methods, however, are labor-intensive, require specialized expertise, and often lack adaptability to rapidly evolving viral variants. Aptamer-based biosensing technologies have emerged as promising alternatives. Aptamers, synthetic single-stranded DNA or RNA oligonucleotides generated via the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) process, exhibit exceptional specificity and high binding affinity, enabling precise recognition of viral proteins. This systematic and critical review synthesizes recent advances in aptamer-integrated biosensing platforms, focusing on electrochemical and optical detection strategies for influenza virus. By comparing sensitivity, specificity, operational simplicity, and translational potential, this review highlights that electrochemical platforms are better suited for point-of-care use due to their speed and simpler instrumentation, while optical platforms offer superior sensitivity for reference laboratory settings. A key finding is that despite two decades of research and remarkable analytical sensitivity (reaching fg/mL levels), the vast majority of platforms have not been validated on authentic clinical specimens or compared with gold-standard molecular methods, explaining why none have entered routine diagnostic workflows. The analysis provides evidence-based insights into which biosensing strategies are most suitable for the development of rapid, reliable, and scalable diagnostic tools against influenza virus, thereby informing future research directions and clinical translation.