MIT researchers developed a groundbreaking super-resolution imaging platform called U-STORM (Upconversion enabled Stochastic Optical Reconstruction Microscopy). Unlike conventional multicolor super-resolution imaging, which requires multiple expensive lasers and meticulous optical alignment, U-STORM can operate with just one near-infared laser. This results in a drastic reduction of an experiment’s complexity.
Image Credit: Courtesy of the researchers.
Scientific Frontline: Extended "At a Glance" Summary: U-STORM (Upconversion-Enabled Stochastic Optical Reconstruction Microscopy)
The Core Concept: U-STORM is a groundbreaking super-resolution imaging platform that allows scientists to visualize molecular structures with sub-angstrom-level precision using a novel class of engineered nanoparticles.
Key Distinction/Mechanism: Unlike conventional multicolor super-resolution microscopy, which requires multiple expensive lasers, meticulous optical alignment, and traditional dyes that fade rapidly, U-STORM operates with a single near-infrared laser. It excites upconverting nanoparticles that blink spontaneously and indefinitely, allowing simultaneous multicolor imaging without the need for complex imaging buffers.
Major Frameworks/Components:
- Upconverting Nanoparticles (UCNPs): Engineered core-shell particles (approximately 10nm in size) that were historically considered completely photostable, but have been successfully coaxed into spontaneous, indefinite "on" and "off" states.
- Sub-Angstrom Localization Precision: Because the particles blink indefinitely, researchers can collect over 88,000 localization events from a single particle, refining the localization precision down to an unprecedented 0.6 Å.
- Single-Laser Near-Infrared Excitation: A simplified optical setup that utilizes one near-infrared laser to simultaneously excite nanoparticles emitting different colors, drastically reducing experimental complexity.
Branch of Science: Chemistry, Nanoscience, Nanotechnology, Optical Physics, and Biological Imaging.
Future Application: The platform establishes a new design principle for lanthanide nanomaterials. It will be used to investigate complex nanoscale protein organizations and cellular signaling pathways, while researchers actively work to expand the color palette and synthesize smaller, brighter particles.
Why It Matters: By overturning the decades-old paradigm that upconverting nanoparticles are non-blinking, U-STORM provides a drastically simpler, cost-effective, and highly accessible route for laboratories worldwide to achieve ultra-high-precision molecular imaging.
Researchers in the lab of Sam Peng, the Pfizer Inc.–Gerald Laubach Career Development Assistant Professor of Chemistry at MIT and a core institute member of the Broad Institute of MIT and Harvard, have developed a groundbreaking super-resolution imaging technology that allows scientists to visualize molecular structures with subangstrom-level localization precision—three orders of magnitude beyond the nanometer limits of standard fluorescent dyes—while drastically simplifying the imaging process.
Unlike traditional dyes that fade rapidly under illumination and limit data collection, the platform, called U-STORM (upconversion-enabled stochastic optical reconstruction microscopy), utilizes a new class of compositionally engineered upconverting nanoparticles (UCNPs) that blink spontaneously and indefinitely.
This work represents a fundamental shift in both optical materials and biological imaging.
Overturning a Decades-Old Paradigm
For decades, the scientific community widely considered upconverting nanoparticles to be completely photostable and nonblinking. Because localization-based super-resolution microscopy techniques like STORM rely entirely on the stochastic “blinking” (switching between “on” and “off” states) of light emitters to distinguish closely packed molecules, UCNPs were historically deemed unsuitable for this type of imaging.
“Our laboratory has long been interested in overcoming these limitations,” says Peng. “Our work began with a question: Can we develop a super-resolution imaging platform that is simultaneously long-term, multicolor, simple to operate, and capable of achieving extremely high localization precision without using imaging buffers or additional optical control?”
By meticulously controlling nanoparticle composition, the MIT and Broad Institute team discovered that these small (~10 nm) core–shell particles could actually be coaxed into spontaneous blinking under continuous near-infrared excitation. Remarkably, this blinking behavior continues indefinitely without the need for complex imaging buffers, oxygen scavengers, or external optical modulation.
U-STORM’s Key Breakthroughs
An angstrom is a tiny unit of measurement used by chemists to measure sizes and distances at the atomic level. U-STORM’s ability to blink indefinitely has afforded researchers the opportunity to collect more than 88,000 localization events from the same particle, sharpening the localization precision down to an unprecedented 0.6 Å.
Unlike conventional multicolor super-resolution imaging, which requires multiple expensive lasers and meticulous optical alignment, U-STORM can operate with just one near-infrared laser, which works to simultaneously excite nanoparticles emitting different colors. This results in a drastic reduction in an experiment’s complexity.
To obtain images with multiple colors, rather than capturing images sequentially over multiple rounds, U-STORM captures multiple colors simultaneously. Researchers have successfully demonstrated this by mapping epidermal growth factor receptor dimers and multimers in biological samples under physiological conditions without any specialized imaging buffers.
Broader Impact
Beyond expanding the boundaries of microscopy, this research establishes an entirely new design principle for lanthanide nanomaterials. The team is already working to expand the color palette, make the particles even smaller and brighter, and deploy U-STORM to investigate complex nanoscale protein organization and cellular signaling pathways.
Ultimately, U-STORM promises to provide laboratories worldwide with an accessible, easy-to-implement, yet incredibly powerful route toward high-precision molecular imaging.
Published in journal: Nature Nanotechnology
Authors: Saptarshi Mandal, Harrison W. Toll, Kaibo Ma, Irmuun Tommy Altankhuyag, Lidao Li, Wanlin Zhang, João F. Shida, and Chunte Sam Peng
Source/Credit: Massachusetts Institute of Technology | Danielle Randall Doughty / Department of Chemistry
Edited by: Scientific Frontline
Reference Number: chm072926_01
.jpg)