New microscope offers unprecedented view of biomolecules

Dual-colour STORM images of COS-7 cells (left) and C. crescentus (R) taken with the new technique © Nature Photonics

Dual-colour STORM images of COS-7 cells (left) and C. crescentus (R) taken with the new technique © Nature Photonics

EPFL scientists have developed a new low-cost microscope with nano-scale resolution and an unprecedented large field-of-view. Overcoming the limitations of similar systems, the new microscope can take gigapixel-sized images of multiple cells and bacteria with nanometer-scale resolution, offering a powerful tool to observe biological processes.

One of the biggest challenges in microscopy is the natural limits of resolution imposed by light diffraction as it goes through the microscope’s lenses and circular apertures. This means that anything smaller than 200 nanometers will appear blurry. When it comes to biological molecules, which can be hundreds of times smaller, this can be a real problem. EPFL scientists have now developed a new low-cost microscopy technique that can image multiple cells at the same time efficiently on a nanoscale resolution. The work is published in Nature Photonics.

Most biological processes take place on the nanoscale, but their effects travel up to the cell’s level, at the microscale — and even beyond. In order to address this difference, microscopy engineers have developed “single-molecule localization microscopy” techniques, which can allow scientists to study cellular features with resolutions around 10 nm. But these techniques tend to have a very constrained field of view and non-uniform image resolution.

The lab of Suliana Manley at EPFL has now developed a new microscopy technique called “flat illumination for field-independent imaging” or FIFI. The system is based on a pair of microlens arrays and uses epi-illumination — that is, the illumination and detection occurs on only one side of the sample. The scientists used FIFI successfully to image multiple cells and bacteria in culture, showing how the system more than quadruples the size of the field-of-view in conventional systems while producing near-gigapixel-sized, nano-scale images of uniformly high quality.

This work was funded by the National Centre of Competence in Research Chemical Biology, the European Research Council (PALMassembly), and


Kyle M. Douglass, Christian Sieben, Anna Archetti, Ambroise Lambert, Suliana Manley. Super-resolution imaging of multiple cells by optimized flat-field epi-illumination. Nature Photonics 10, 705–708 (17 October 2016). DOI: 10.1038/nphoton.2016.200.