Resonance Energy Transfer‐Driven Lasing Mode Switching Visualizes DNA Zippering in Real Time

ABSTRACT Real‐time DNA hybridization analysis is crucial for CRISPR editing verification and therapeutics development, yet remains challenging without sacrificing speed or simplicity. Here, we develop a coupler‐free microlaser platform that integrates resonance energy transfer (RET) with whispering‐gallery‐mode (WGM) lasing to transduce hybridization‐dependent RET into gain‐competition‐mediated lasing‐mode switching. In this system, RET encompasses short‐range non‐radiative Förster resonance energy transfer (FRET) between surface‐proximal donor–acceptor pairs and cavity‐mediated radiative energy transfer through resonant WGM photons. Using DNA‐grafted microspheres as laser probes, the system enables low‐threshold lasing under free‐space pumping. Hybridization‐induced acceptor recruitment progressively redistributes the donor–acceptor gain balance, inducing discrete switching between adjacent WGM resonances with a characteristic spacing of Δλ = 3.97 nm that serves as a built‐in spectral ruler. This self‐referencing mechanism monitors hybridization across 10–22 base oligonucleotides and identifies base‐pair mismatches, operating under physiological conditions while revealing length‐dependent kinetics. while revealing length‐dependent kinetics. The design establishes a scalable route for dynamic nucleic acid studies, positioning it as a versatile tool for molecular diagnostics and drug discovery.