Förster Resonance Energy Transfer-Based Selective Detection of Influenza Viruses Using N-Doped Sialic Acid Carbon Dots

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Abstract
We report the rational design and synthesis of nitrogen-doped sialic acid-derived carbon dots (SiaMPDA CDs) with excitation-independent green emission and high quantum yield and demonstrate their application as efficient Förster resonance energy transfer (FRET) donors for the selective detection of influenza A virus (IAV) subtypes. The surface functionalization of the CDs with sialic acid moieties enables specific molecular recognition of the viral hemagglutinin (HA) protein via multivalent hydrogen-bonding interactions. In combination with Rhodamine B (RhB) as an acceptor, the SiaMPDA–RhB pair exhibits efficient FRET under native conditions. Upon interaction with IAV (H3N2 and H1N1), the FRET system displays anomalous spectral behavior characterized by a simultaneous increase in both donor and acceptor emission intensities without any spectral shift. Mechanistic investigations suggest the formation of a ternary IAV–SiaMPDA–RhB complex, wherein long-range charge transfer coupled with FRET governs the observed fluorescence response. Control experiments with proteins, membrane vesicles, and liposomes confirm that the signal specificity arises from targeted interactions between the sialic acid functionalities of the CDs and the viral surface proteins. The sensing platform enables selective and sensitive detection of IAV subtypes in the picomolar range, comparable to existing carbon dot-based detection systems. These findings establish N-doped sialic acid carbon dots as promising nanoscale probes for virus detection and provide insights into charge-transfer-coupled FRET mechanisms in complex bionano interfaces.
Funding Information
  • Prime Minister Research Fellowship
  • IIT Kanpur for lab development grants

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