Near-infrared long lifetime upconversion nanoparticles for ultrasensitive microRNA detection via time-gated luminescence resonance energy transfer
Suyeon Kim, Yeonkyung Park, Jiwoo Han, Hansol Kim, Hyowon Jang, Sohyung Kim, Dongkyu Kang, Min‐Young Lee, Byeong‐Ho Jeong, Yuree Byun, Eun‐Kyung Lim, Juyeon Jung, Taejoon Kang, Joonseok Lee
Abstract
Upconversion nanoparticle (UCNP)-based luminescence resonance energy transfer (LRET) biosensing offers advantages such as wash-free detection and precise biomolecule quantification. However, its sensitivity remains limited due to continuous energy transfer in co-doped UCNPs during LRET. Here we present a time-gated LRET strategy using near-infrared (NIR) long-lived luminescent UCNP donors (L-TG-LRET), achieving an 8-fold increase in luminescence lifetime without compromising emission intensity. This prolonged energy migration and transfer pathway significantly enhances sensitivity by preventing rapid Tm3+ reactivation during LRET to IRDye800 acceptors. Applying this approach to microRNA (miRNA) detection, we achieve a 17.9-fold higher sensitivity than conventional steady-state methods. Furthermore, the L-TG-LRET successfully quantifies miRNA expression in cancer cells, plasma, and exosomes, enabling the differentiation of cancer patients from healthy donors. Notably, this approach outperforms polymerase chain reaction in detecting low-abundance exosomal miRNAs. These results highlight the potential of L-TG-LRET system as a valuable tool for sensitive biomolecular detection in clinical diagnostics. Kim, Park, and colleagues present near-infrared long-lifetime upconversion nanoparticles combined with time-gated detection. These nanoparticles allow for improved performance of luminescence-based biosensing for sensitive and accurate microRNA analysis in cancer diagnostics.