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<p>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 Tm<sup>3+</sup> 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.</p>

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Near-infrared long lifetime upconversion nanoparticles for ultrasensitive microRNA detection via time-gated luminescence resonance energy transfer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月14日

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  • 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

摘要

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.