Quantum dot-FRET viral biosensors: Materials, surface chemistry, and recognition architectures

Viral outbreaks continue to require diagnostic platforms that are sensitive, selective, rapid, and compatible with decentralized use. Quantum dot (QD)-based Förster resonance energy transfer (QD-FRET) biosensors offer a promising route because viral recognition can be translated into ratiometric optical signals through nanoscale changes in donor-acceptor distance, orientation, and local interfacial environment. However, QD-FRET performance is not determined by photophysics alone. It emerges from the coupled behavior of QD composition, core/shell architecture, ligand-shell packing, hydration, protein-corona formation, bioconjugation geometry, and assay format. This review examines QD-FRET viral biosensors from an interfacial physical chemistry perspective. First, the photophysical basis of QD-mediated energy transfer is summarized with emphasis on Förster distance, donor lifetime, spectral overlap, multivalency, and distance heterogeneity. QD materials are then compared in terms of composition, shell engineering, trap-mediated recombination, toxicity, and colloidal stability. Particular attention is given to surface functionalization strategies, including ligand exchange, compact thiol ligands, polymer and silica encapsulation, zwitterionic and PEG-based antifouling layers, and matrix-induced interfacial restructuring. Biochemical recognition layers based on nucleic acids, antibodies, protein binders, receptor-mimetic peptides, aptamers, and glycans are treated as distinct nanoscale architectures that control spacing, orientation, accessibility, and matrix tolerance. Representative mechanisms are then analyzed across hybridization-induced, CRISPR-cleavage-enabled, immuno-FRET, plasmon- and 2D-material-assisted, time-gated, chemiexcited, and whole-virus or pseudo-virion assemblies. Across these systems, reported limits of detection are interpreted together with matrix complexity, amplification chemistry, readout mode, donor-acceptor geometry, and stability controls. Progress toward robust QD-FRET viral diagnostics will require reproducible QD materials, standardized characterization, tighter control of ligand and recognition-layer heterogeneity, and integration with field-compatible point-of-care formats.