Achieving Cross Time-Domain Multiplexed Signal Cascade and Cancer Exosomes Identification by Bridging Long Lifetime Phosphor to NIR-II Lanthanide Energy Transfer.

Designing lanthanide luminescence lifetime sensors in the second near-infrared (NIR-II) window holds great potentials for physiological studies. However, the single lifetime signal is confined to one or two orders of magnitude of signal variation, which limits the sensitivity of lifetime probes. In this study, a lifetime cascade system, i.e., ZGO:Mn, Eu-DNA-1/TCPP-PEI 70K @Yb-Apt EpCAM , with a variety of signals (τ m , τ n , τ µ , τ m /τ n and τ m /τ µ ) is constructed for exosome identification using time-domain multiplexing. The sensitized ligand TCPP acts as both target-modulated switch and a bridge for connecting long lifetime ZGO:Mn, Eu-DNA-1 emitter to lanthanide Yb 3+ . This drives successive dual-path energy transfer and forms two D (donor) -A (acceptor) pairs. The lifetime variation is dominantly modulated by arranging TCPP as energy intermediate relay to covert milliseconds to nanoseconds to microseconds. It enables a broad lifetime range of six orders of magnitude. The presence of exosome specifically recognizes aptamers on TCPP-PEI 70K @Yb-Apt EpCAM to impede D-A pairs and reverse multiplexed response signals of the lifetime cascade system. The ratio lifetime signals τ m /τ n and τ m /τ µ achieve prominent exosome quantification and exosome type differentiation attributed to signal amplification. The cascade system relying on lifetime criteria can realize precise quantization and provide an effective strategy for subsequent physiological study.