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

Author

Listed:
  • Morgane Loretan

    (University of Fribourg)

  • Mariano Barella

    (University of Fribourg
    University of Fribourg)

  • Nathan Fuchs

    (University of Fribourg)

  • Samet Kocabey

    (University of Fribourg
    University of Fribourg)

  • Karol Kołątaj

    (University of Fribourg
    University of Fribourg)

  • Fernando D. Stefani

    (Universidad de Buenos Aires)

  • Guillermo P. Acuna

    (University of Fribourg
    University of Fribourg)

Abstract

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.

Suggested Citation

  • Morgane Loretan & Mariano Barella & Nathan Fuchs & Samet Kocabey & Karol Kołątaj & Fernando D. Stefani & Guillermo P. Acuna, 2025. "Direct single-molecule detection and super-resolution imaging with a low-cost portable smartphone-based microscope," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63993-z
    DOI: 10.1038/s41467-025-63993-z
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