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Gulbenkian group claims microscopy advance ‘beyond conventional resolution’

16 Nov 2023

Enhanced Super-Resolution Radial Fluctuations improves on live-cell imaging, with unparalleled clarity.

Researchers at the Gulbenkian Science Institute, based in Oeiras, Portugal, have made what they are calling “an innovative breakthrough in microscopy” called eSRRF, which stands for enhanced Super-Resolution Radial Fluctuations.

This novel method, described this week in Nature Methods, furthers our understanding of biological systems through live-cell imaging, offering a glimpse into the microscopic world with unparalleled clarity and precision.

The Gulbenkian statement says, “Imagine having a microscope that magnifies and enhances the tiniest details, revealing a world beyond the limits of conventional resolution. That’s precisely what eSRRF brings to the scientific forefront—an upgraded super-resolution magic wand for microscopes.”

It continues, “Building upon the success of the SRRF method, eSRRF is not just an evolution; it’s a revolution. It takes microscopic imaging to the next level, delivering enhanced fidelity to the underlying structures and resolutions. eSRRF features automated data-driven parameter optimization. It determines the optimal number of frames needed for reconstruction, providing scientists with efficient imaging experience.”

eSRRF can be teamed up with multi-focus microscopy, promising an era of 3D super-resolution imaging. This could enable the capture of volumetric snapshots of live cells at a rate of approximately one volume per second.

Considering research openness and easy usability, eSRRF is designed with user-friendliness, integrating seamlessly with various microscopy techniques and biological systems, and, says the Gulbenkian, “researchers can now explore the microscopic realm without technological barriers”.

Hannah Heil, the paper’s first author, commented, “eSRRF opens up new possibilities in live-cell imaging. It’s not just about enhancing image resolution; eSRRF empowers researchers to optimize results based on quantitative image quality measures. Our method provides researchers with a dynamic tool that adapts to their needs, making the invisible visible.”

‘Window into the future’

Ricardo Henriques, leading the Optical Cell Biology research group at the IGC, added that the new method “is a window into the future of scientific exploration. eSRRF can potentially revolutionize several fields, from biology to medicine, paving the way for discoveries that were once beyond our visual reach.

This initiative was supported by The Gulbenkian Foundation, the European Research Council, the European Commission, the European Molecular Biology Organization, the Wellcome Trust, Fundação para a Ciência e Tecnologia, and the Chan Zuckerberg Initiative.

Nature Methods paper abstract

The Nature Methods paper abstract reads:

“Live-cell super-resolution microscopy enables the imaging of biological structure dynamics below the diffraction limit. Here we present enhanced super-resolution radial fluctuations (eSRRF), substantially improving image fidelity and resolution compared to the original SRRF method. eSRRF incorporates automated parameter optimization based on the data itself, giving insight into the trade-off between resolution and fidelity. We demonstrate eSRRF across a range of imaging modalities and biological systems.

“Notably, we extend eSRRF to three dimensions by combining it with multifocus microscopy. This realizes live-cell volumetric super-resolution imaging with an acquisition speed of ~1 volume per second. eSRRF provides an accessible super-resolution approach, maximizing information extraction across varied experimental conditions while minimizing artifacts. Its optimal parameter prediction strategy is generalizable, moving toward unbiased and optimized analyses in super-resolution microscopy.”

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