Plasmon-enhanced FRET biosensor based on Tm³⁺/Er³⁺ co-doped core-shell upconversion nanoparticles for ultrasensitive virus detection

Outbreaks of infectious viruses offer a formidable challenge to public healthcare systems and early detection of viruses is essential for preventing virus propagation. In this work, an ultrasensitive plasmon-enhanced fluorescence resonance energy transfer (FRET) biosensor based on core-shell upconversion nanoparticle (csUCNP) and gold nanoparticle (AuNP) for accurate detection of SARS-CoV-2 viral RNA is presented. In this biodetection assay, the Tm³⁺/Er³⁺ co-doped csUCNP NaGdF₄:Yb/Tm@NaYF₄:Yb/Er acts as an energy donor and AuNP serves as an energy acceptor. The upconversion emission of Tm³⁺ and the design of the core-shell structure led to a simultaneous surface plasmon effect of AuNP. The localized surface plasmon resonance (LSPR) arising from collective oscillations of free electrons significantly enhanced FRET efficiency between Er³⁺ and AuNP. The as-prepared biosensor obtained a limit of detection (LOD) as low as 750 am, indicating that the integration of FRET and surface plasmon into one biodetection assay significantly boosted the sensitivity of the biosensor. In addition, samples extracted from clinical samples are also utilized to validate the effectiveness of the biosensor. Therefore, this innovative plasmon-enhanced FRET biosensor based on Tm³⁺/Er³⁺ co-doped csUCNP may pave the way for rapid and accurate biodetection applications.