Researchers from the lab of Sam Peng, who holds the Pfizer Inc. – Gerald Laubach Career Development Assistant Professorship in Chemistry at MIT and is a key member of the Broad Institute of MIT and Harvard, have invented a revolutionary super-resolution imaging method. This technology allows for the visualization of molecular structures with sub-angstrom precision, surpassing the typical nanometer limits of standard fluorescent dyes by three magnitudes, while significantly simplifying the imaging process.<\/p>\n
Unlike conventional dyes that quickly degrade under light, limiting data collection, the U-STORM (Upconversion enabled Stochastic Optical Reconstruction Microscopy) platform uses a new kind of engineered upconverting nanoparticles (UCNPs) that spontaneously and indefinitely blink. This advancement marks a significant change in both optical materials and biological imaging. Details of the study appeared in Nature Nanotechnology on July 27.<\/p>\n
For many years, scientists believed that upconverting nanoparticles were entirely photostable and non-blinking, making them unsuitable for localization-based super-resolution microscopy methods like STORM. These techniques depend on the random “blinking” of light emitters to differentiate closely-packed molecules. “Our lab has been focused on overcoming these challenges,” Peng states. “We questioned whether it was possible to create a super-resolution imaging platform that is long-lasting, multicolor, simple to use, and achieves very high localization precision without additional imaging buffers or optical controls.”<\/p>\n
By carefully controlling the composition of nanoparticles, the MIT and Broad Institute team found that small (~10nm) core-shell particles can be made to blink spontaneously under continuous near-infrared light. This blinking persists indefinitely, eliminating the need for complex imaging buffers, oxygen scavengers, or external optical modulation.<\/p>\n
An angstrom, a small unit used in chemistry to measure atomic sizes and distances, is now achievable with U-STORM’s indefinite blinking, allowing researchers to gather over 88,000 localization events from the same particle, achieving an unprecedented localization precision of 0.6 \u00c5. Unlike traditional multicolor super-resolution imaging, which requires various costly lasers and precise optical alignment, U-STORM operates using a single near-infrared laser, simultaneously exciting nanoparticles that emit different colors, thus reducing the experiment’s complexity.<\/p>\n
Instead of capturing images sequentially in multiple rounds for multicolor imaging, U-STORM captures multiple colors at once. The researchers demonstrated this by mapping epidermal growth factor receptor dimers and multimers in biological samples under physiological conditions without needing specialized imaging buffers.<\/p>\n
This research not only pushes the limits of microscopy but also introduces a new design approach for lanthanide nanomaterials. The team is working to expand the color range, make the particles smaller and brighter, and use U-STORM to explore complex nanoscale protein structures and cellular signaling pathways. U-STORM offers laboratories around the world a straightforward yet powerful tool for high-precision molecular imaging.<\/p>\n