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

Morgane Loretan1, Mariano Barella2,3, Nathan Fuchs1

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Summary

We developed a low-cost, portable smartphone fluorescence microscope for direct single-molecule detection. This portable device enables sensitive molecular detection for point-of-care diagnostics and field applications.

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Area of Science:

  • Biophysics
  • Microscopy
  • Point-of-Care Diagnostics

Background:

  • Single-molecule detection offers ultimate sensitivity but typically requires expensive, lab-based equipment.
  • Existing methods often rely on signal amplification, adding complexity and cost.

Purpose of the Study:

  • To present a low-cost, portable smartphone-based fluorescence microscope for direct single-molecule detection.
  • To demonstrate the adaptability and broad spectral range of the smartphone microscope.
  • To illustrate its potential for point-of-care applications.

Main Methods:

  • Leveraged smartphone image sensors and data processing capabilities.
  • Developed a portable fluorescence microscope adaptable to various smartphones.
  • Utilized single-molecule localization microscopy (SMLM) for cellular imaging.
  • Implemented a single-molecule bioassay for RNA detection.

Main Results:

  • Successfully detected single-molecule fluorescence directly without amplification.
  • Demonstrated single-molecule measurements on DNA origami models.
  • Performed super-resolution microscopy on cells.
  • Validated its potential as a point-of-care device for RNA detection.

Conclusions:

  • The smartphone-based fluorescence microscope offers a low-cost, portable solution for single-molecule detection.
  • This technology enables innovative applications in distributed or personalized assays.
  • Potential applications include digital bioassays, POC diagnostics, field studies, and STEM education.