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 () and Joonseok Lee ()
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Suyeon Kim: Hanyang University
Yeonkyung Park: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Jiwoo Han: Hanyang University
Hansol Kim: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Hyowon Jang: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Sohyung Kim: Hanyang University
Dongkyu Kang: Hanyang University
Min-Young Lee: Korea Institute of Materials Science (KIMS)
Byeong-Ho Jeong: Sungkyunkwan University (SKKU) School of Medicine
Yuree Byun: Samsung Medical Center
Eun-Kyung Lim: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Juyeon Jung: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Taejoon Kang: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Joonseok Lee: Hanyang University

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-62802-x

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