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

Morgane Loretan, Mariano Barella (), Nathan Fuchs, Samet Kocabey, Karol Kołątaj, Fernando D. Stefani () and Guillermo P. Acuna ()
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Morgane Loretan: University of Fribourg
Mariano Barella: University of Fribourg
Nathan Fuchs: University of Fribourg
Samet Kocabey: University of Fribourg
Karol Kołątaj: University of Fribourg
Fernando D. Stefani: Universidad de Buenos Aires
Guillermo P. Acuna: University of Fribourg

Nature Communications, 2025, vol. 16, issue 1, 1-12

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-63993-z

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