Seeing the tiniest structures inside cells, down to individual molecules, is one of the great frontiers of biology.
A powerful method called MINFLUX already does this exceptionally well. MINFLUX has pushed the limit of an optical microscope's resolution to the molecular scale, localising a molecule with nanometer-scale precision by shining a special laser pattern on the molecules and measuring the amount of fluorescence emitted by the molecules for different positions of the laser beam. But while MINFLUX is powerful, it’s also notoriously complex: it needs to scan repeatedly over smaller and smaller areas to improve accuracy, which makes it slower and more challenging to use.
Now, in a study published in Light: Science & Applications , a team led by Dr. Giuseppe Vicidomini at the Istituto Italiano di Tecnologia (IIT) in Genoa, Italy, has unveiled ISM-FLUX: a streamlined, smarter version of MINFLUX that keeps the resolution but ditches the complexity.
The secret? An asynchronous read-out single-photon-avalanche diode (SPAD) array detector - an advanced, event-based small camera that detects single photons with incredible precision. By replacing the traditional single-pixel detector with a 5×5 SPAD array, ISM-FLUX captures spatiotemporal information from fluorescence photons otherwise lost. This change allows the system to localise molecules with a few nanometers of precision over a much larger area without losing accuracy and eliminates the need for repeated scanning steps. The team validated ISM-FLUX using fluorescent molecules and DNA nanostructures, resolving distances as small as 6 nanometres—the result: a faster, more user-friendly setup with the potential to transform MINFLUX.
ISM-FLUX is the natural evolution of MINFLUX—a powerful upgrade that turns complexity into accessibility. As Vicidomini’s team puts it, there's no reason not to equip every MINFLUX system with a SPAD array. This innovation brings the team one step closer to their mission: “A SPAD array detector in every laser-scanning microscope.” With ISM-FLUX, the door to molecular-scale imaging in biology just opened wider.
Light Science & Applications
Array Detection Enables Large Localisation Range for Simple and Robust MINFLUX