Researchers have developed a groundbreaking technique called ONE (One-step nanoscale Expansion) microscopy that allows for the 3D visualization of individual proteins using a conventional light microscope. This revolutionary method, which was named one of the “seven technologies to watch in 2024” by Nature, offers unprecedented opportunities for early detection and treatment of protein-related diseases like Parkinson’s disease.

Unlocking Nanoscale Protein Structures
The groundbreaking ONE microscopy technique, developed by researchers at the University Medical Center Göttingen (UMG) in Germany, has the potential to revolutionize the way we visualize and understand the three-dimensional structure of proteins. Traditionally, this level of detail has only been possible using expensive and specialized equipment like electron microscopes and X-ray crystallography.
The key innovation of ONE microscopy is its ability to expand the sample volume up to 15 times, causing the individual proteins to move apart and become larger, while retaining their spatial arrangement. This allows researchers to image these nanoscale structures using a conventional light microscope, which is significantly more accessible and cost-effective than advanced structural biology methods. By combining this sample expansion with targeted fluorescent labeling and artificial intelligence-powered image analysis, the scientists have succeeded in reconstructing 3D protein structures from 2D fluorescence images.
Tackling Protein Misfolding Diseases
One of the most promising applications of ONE microscopy is its potential to aid in the early detection and treatment of protein-related diseases, such as Parkinson’s disease. These diseases are often characterized by the misfolding and aggregation of specific proteins, which can lead to the death of cells and the onset of debilitating symptoms.
Using ONE microscopy, researchers have already been able to image and classify the protein aggregates associated with Parkinson’s disease in cerebrospinal fluid samples from patients. This breakthrough could enable a visual diagnosis of the disease based on easily accessible biological samples, potentially allowing for earlier intervention and more personalized treatment plans before the brain sustains significant damage.
Democratizing High-Resolution Microscopy
One of the most remarkable aspects of ONE microscopy is its accessibility and cost-effectiveness. Unlike super-resolution techniques that require expensive and specialized equipment, ONE microscopy can be carried out in any laboratory with a conventional light microscope, making it a game-changer for the field of microscopy.
The researchers have even provided the necessary software as a free open-source package, further lowering the barriers to entry for this revolutionary technique. This democratization of high-resolution imaging has the potential to accelerate scientific discoveries, foster collaborations, and empower researchers worldwide to explore the intricate details of cellular structures and biochemical processes with unprecedented clarity.