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High throughput analysis of rare nanoparticles with deep-enhanced sensitivity via unsupervised denoising

Author

Listed:
  • Yuichiro Iwamoto

    (Shibuya)

  • Benjamin Salmon

    (University of Birmingham)

  • Yusuke Yoshioka

    (Shinjuku)

  • Ryosuke Kojima

    (Bunkyo)

  • Alexander Krull

    (University of Birmingham)

  • Sadao Ota

    (Shibuya)

Abstract

The large-scale multiparametric analysis of individual nanoparticles is increasingly vital in the diverse fields of biology, medicine, and materials science. However, the current methods struggle with the tradeoff between measurement scalability and sensitivity, especially when identifying rare nanoparticles in heterogeneous mixtures. By developing and combining an unsupervised deep learning-based denoising method and an optofluidic device tuned for nanoparticle detection, we realize a nanoparticle analyzer that simultaneously achieves high scalability, throughput, and sensitivity levels; we name this approach “Deep Nanometry” (DNM). DNM detects polystyrene beads with a detection of limit of 30 nm at a throughput of over 100,000 events/second. The sensitive and scalable DNM directly detects rare target extracellular vesicles (EVs) in non-purified serum, making up as little as 0.002% of the 1,214,392 total particles. Moreover, DNM accurately and sufficiently counts diagnostic marker EVs present in only 0.93% and 0.17% of particle detections in sera of colorectal cancer patients and healthy controls, demonstrating its potential application to the early detection of colorectal cancer.

Suggested Citation

  • Yuichiro Iwamoto & Benjamin Salmon & Yusuke Yoshioka & Ryosuke Kojima & Alexander Krull & Sadao Ota, 2025. "High throughput analysis of rare nanoparticles with deep-enhanced sensitivity via unsupervised denoising," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56812-y
    DOI: 10.1038/s41467-025-56812-y
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    References listed on IDEAS

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    1. Yusuke Yoshioka & Nobuyoshi Kosaka & Yuki Konishi & Hideki Ohta & Hiroyuki Okamoto & Hikaru Sonoda & Ryoji Nonaka & Hirofumi Yamamoto & Hideshi Ishii & Masaki Mori & Koh Furuta & Takeshi Nakajima & Hi, 2014. "Ultra-sensitive liquid biopsy of circulating extracellular vesicles using ExoScreen," Nature Communications, Nature, vol. 5(1), pages 1-8, May.
    2. Lucas von Chamier & Romain F. Laine & Johanna Jukkala & Christoph Spahn & Daniel Krentzel & Elias Nehme & Martina Lerche & Sara Hernández-Pérez & Pieta K. Mattila & Eleni Karinou & Séamus Holden & Ahm, 2021. "Democratising deep learning for microscopy with ZeroCostDL4Mic," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
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