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<p>Detecting single molecules, which represents the ultimate level of sensitivity, is typically achieved with research-grade equipment. Here we present a low-cost, portable smartphone-based fluorescence microscope capable of detecting single-molecule fluorescence directly, i.e., without the need for any signal amplification. The setup leverages the image sensors and data handling capacity of mass-produced smartphones, it is adaptable to different smartphones and capable of detecting single molecules across the visible spectral range. We showcase this capability through single-molecule measurements on DNA origami models and super-resolution microscopy of cells by single-molecule localization microscopy. Last, we illustrate its potential as a point-of-care (POC) device by implementing a single-molecule bioassay for RNA detection. This development paves the way for innovative applications of massively distributed or personalized assays with single-molecule sensitivity in various fields such as digital bioassays, POC diagnostics, field expeditions, STEM outreach, and life science education.</p>

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Direct single-molecule detection and super-resolution imaging with a low-cost portable smartphone-based microscope

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月8日

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  • Morgane Loretan,
  • Mariano Barella,
  • Nathan Fuchs,
  • Samet Kocabey,
  • Karol Kołątaj,
  • Fernando D. Stefani,
  • Guillermo P. Acuna

摘要

Detecting single molecules, which represents the ultimate level of sensitivity, is typically achieved with research-grade equipment. Here we present a low-cost, portable smartphone-based fluorescence microscope capable of detecting single-molecule fluorescence directly, i.e., without the need for any signal amplification. The setup leverages the image sensors and data handling capacity of mass-produced smartphones, it is adaptable to different smartphones and capable of detecting single molecules across the visible spectral range. We showcase this capability through single-molecule measurements on DNA origami models and super-resolution microscopy of cells by single-molecule localization microscopy. Last, we illustrate its potential as a point-of-care (POC) device by implementing a single-molecule bioassay for RNA detection. This development paves the way for innovative applications of massively distributed or personalized assays with single-molecule sensitivity in various fields such as digital bioassays, POC diagnostics, field expeditions, STEM outreach, and life science education.