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At the meeting point of Switzerland, France and Germany, Basel is a hub for biotechnology and pharma. It is not surprising, therefore, that our Super-Resolution Summit there was heavily focused on new technological development in super-resolution microscopy. Two of the recurring themes in this summit were PAINT (point accumulation for imaging in nanoscale topography) and MINFLUX (Minimal photon fluxes).
PAINT was first introduced in 2006 and is evolving ever since. Two of our speakers discussed new developments in PAINT. Dr Kimberly Cramer from Massive Photonics gave a thorough introduction to DNA-PAINT and introduced RESI, a DNA-PAINT approach of sequential imaging, each time with probes of different sequences, so that the scientist can image multiple targets in the same sample. She demonstrated the power of this method when she showed an image of 30 different targets!
Dr Roderick Tas from Eindhoven University of Technology also discussed PAINT, and he introduced two different derivatives of the technology, peptide-based PAINT and qPAINT: here, instead of using labeled DNA strands, scientists can use a protein-peptide pair, where the fluorescently-labeled protein binds a docking peptide, conjugated to a target of interest. This pair can be expressed by the cells and no exogenous introduction of fluorophores is needed. Dr Tas also discussed qPAINT, a method to get quantitative information on the number of labeled targets, based on the known number of probes and the kinetics of the binding. While this is considered simpler with DNA-based probes, Dr Tas aims to do this with his protein-peptide pair.
Another prominent technique in this Summit was MINFLUX, a super-resolution technology that is a hybrid of SMLM and STED: It is based on a donut-shaped laser beam that determines the localizations of individual blinking fluorophores. It is very sensitive and can provide precision of 3 nm, which is why preparing the samples and their imaging is often very challenging and requires very precise conditions.
Dr Javier Casares-Arias walked us through his experience with MINFLUX in the single-cell facility of ETH Zurich, and he showed some remarkable images taken with their microscope, including a beautiful 3D image of a retina organoid.
Dr Richard Lincoln from the Max Planck Institute for Medical Research presented an interesting strategy to develop new fluorophores, based on the concept of UV-induced chemical changes to small molecules that convert them into fluorophores. These molecules can be introduced to cells and activated only when needed, making them compatible with live-cell imaging.
Our final two speakers, Prof Bernd Rieger from the Technical University in Delft and Dr Willi Leopold Stepp from the EPFL in Lausanne, shared new software advances in super-resolution. Prof Rieger described how they apply concepts in physics to questions structural biology, and how image analysis tools from electron microscopy can also be beneficial in SMLM. Meanwhile, Dr Stepp talked about his work with AI models that can predict sparse biological events, such as mitochondrial fission, and use them to apply high-power imaging only at specific time points, while imaging at lower power levels during the rest of the time. This approach is faster and gentler on live cells.
In addition to these inspiring talks, we also held live demos of our extracellular vesicle range, namely EV Profiler 2, Auto EV and Aplo Flow, as well as of our dSTORM in Cells kits. Our software experts were around to discuss what’s new on CODI and how it can be applied in super-resolution research. We had such a great time with people from diverse backgrounds, ranging from physics to pharma, and we can’t wait to see everyone soon!
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