In the space of two weeks in June 2026, two separate groups published results that, taken together, hint at a broader transformation in how scientists visualize the smallest structures of matter.
One paper came from the MIT laboratory of Edward Boyden, a pioneer of expansion microscopy. The other came from Fudan University in Shanghai, where physicists have been wrestling with an air-sensitive quantum material. Neither team was working on the other’s problem. But both solved the same fundamental challenge: how to see what was previously impossible to see, at a scale that matters.
Making the invisible visible, by making it bigger
The idea behind expansion microscopy is elegant in its simplicity. Biological samples are embedded in a swellable hydrogel, similar to the material in disposable diapers, and then physically expanded before imaging, so that structures too small for a conventional light microscope to resolve become large enough to see.
Since Boyden’s group first introduced the technique in 2015, it has become a standard tool in neuroscience and cell biology, with successive iterations pushing expansion from roughly 4-fold to about 20-fold in each dimension.
The new preprint from Boyden’s team, posted on bioRxiv on June 1 (DOI: 10.64898/2026.05.31.729018), shatters that ceiling. The method, called thousandfold expansion microscopy (1000ExM), uses a four-network interpenetrating hydrogel architecture that enables expansion to more than 1,000 times in each linear dimension, a billion-fold in volume.
The technical innovation is chemical. Amino acid side chains, the chemical “handles” protruding from the backbone of every protein, are anchored to the swellable polymer. Then the backbone amide bonds themselves are cleaved, freeing individual amino acid residues while preserving their three-dimensional arrangement within the hydrogel. When the hydrogel swells, the residues move apart. At 1,000x expansion, the distance between adjacent amino acids grows from the native 0.38 nanometers (nm) to approximately 380 nm, well above the roughly 200 nm diffraction limit of a standard light microscope.
The team validated the method against structures with known atomic coordinates. They reconstructed green fluorescent protein (GFP) at approximately 1.2 nm resolution from thousands of snapshots, matching the known 0.19 nm X-ray structure with sufficient fidelity to identify the positions of individual amino acids. A nanobody (12 kDa) and the 9-amino-acid mCLING peptide were similarly resolved. The method works on a standard confocal microscope, no super-resolution optics, no specialized illumination, no cryogenic temperatures.
Protecting a quantum surface from the air
The second advance addresses a different kind of resolution problem. MnBi₂Te₄ (MBT) is the only known intrinsic magnetic topological insulator, a material whose interior is electrically insulating but whose surface conducts electricity in a way that is protected by both topology and magnetism. This makes it a candidate platform for topological quantum computing and the study of exotic states such as the quantum anomalous Hall effect and axion insulator physics.
But MBT has a problem. Its surface, where all the interesting physics lives, degrades almost instantly in ambient conditions. Exposed to air, the topmost atomic layers collapse from the intrinsic septuple-layer structure (Te-Bi-Te-Mn-Te-Bi-Te, seven atoms thick) into a different, degraded quintuple-layer arrangement similar to Bi₂Te₃. Every previous transmission electron microscopy (TEM) study had imaged only this damaged surface, leaving open the question of what the pristine material actually looks like.
The Fudan University team, led by Yuanbo Zhang and Wei Ruan and described in Chinese Physics Letters (DOI: 10.1088/0256-307X/43/5/050713), solved the problem with an encapsulation strategy. They exfoliated MBT flakes and immediately capped them with hexagonal boron nitride (hBN) or another MBT flake, all inside an argon-filled glovebox, never exposed to air. The cap protected the surface during focused-ion-beam sample preparation and during TEM imaging itself.
The result was the first atomic-resolution images of the intrinsic septuple-layer structure of MBT. Protected surfaces retained the pristine arrangement; unprotected surfaces collapsed to the degraded structure within minutes.
The common thread
These two results address fundamentally different scales and different scientific domains, one works with individual protein residues in biological tissue, the other with atomic lattice planes in a quantum solid. But both are examples of a theme that is emerging across microscopy in 2026: the barriers that once limited our ability to see the very small are falling, not through incremental improvement of instruments, but through clever sample preparation.
In the Boyden group’s case, the innovation is chemical, a hydrogel that physically expands the sample to bypass the diffraction limit without exotic optics. In the Fudan group’s case, the innovation is environmental, an inert-gas encapsulation protocol that preserves a fragile surface that would otherwise destroy itself before it could be imaged.
Both approaches are generalizable. Expansion microscopy has already been applied across cell biology and neuroscience; 1000ExM extends its reach to molecular-scale protein structure determination with a standard lab microscope. The encapsulation protocol for MBT is being adapted to other air-sensitive 2D quantum materials, many of which have similarly fragile surfaces hiding similarly interesting physics.
The result is a moment when the window into the very small, in both living and solid systems, is widening faster than it has in decades. Imaging at the scale of individual atoms in a quantum material and individual amino acids in a protein, once the exclusive domain of synchrotrons and cryo-electron microscopes costing tens of millions of dollars, is becoming possible with benchtop instruments and careful chemistry.
Sources:
Nature, “Making samples one billion times bigger lets simple microscopes pinpoint amino acids,” June 2026.
Chinese Physics Letters 43(5), 050713 (2026), DOI: 10.1088/0256-307X/43/5/050713, “Encapsulation-Assisted TEM Resolves the Intrinsic Surface Structure of 2D Material MnBi₂Te₄” by Luo, Gao, Huang et al.
Disclosure: The thousandfold expansion microscopy result is based on a bioRxiv preprint (DOI: 10.64898/2026.05.31.729018) that has not yet undergone peer review.