A team of engineers from the Massachusetts Institute of Technology (MIT) has devised a new nanoimaging technique that uses an ordinary light microscope to view viruses and other biological samples at the nanometer scale.
The new nanoimaging method, which is expected to allow scientists to image viruses and even single biomolecules, builds on expansion microscopy - an imaging technique that improves the resolution of the resulting image by physically enlarging the organism or the biomolecule itself, usually through the use of a hydrogel.
In the new nanoimaging method, researchers developed a new kind of hydrogel that is better at maintaining the uniformity of the subject's configuration. This, in turn, makes the setup provide greater accuracy in imaging subjects in the nanoscale.
"If you could see individual molecules and identify what kind they are, with single-digit-nanometer accuracy, then you might be able to actually look at the structure of life. And structure, as a century of modern biology, has told us, governs function," says Edward Boyden, senior author of the study and the Y. Eva Tan Professor in Neurotechnology at MIT.
Researchers detail the new nanoimaging technology in the latest Nature Nanotechnology in an article titled "A highly homogeneous polymer composed of tetrahedron-like monomers for high-isotropy expansion microscopy."
Cost-Effective Technique Without Resolution Losses
The MIT Boyden lab, who made the new study, was also behind the proposal of expansion microscopy back in 2015. Since then, the technique has been used by several laboratories around the world. The same lab has also developed techniques for labeling proteins, RNA, and other biomolecules to make imaging easier after enlarging them in the process.
Now that the expansion microscopy is widely-adopted worldwide, Boyden recognizes the need for an easier and more cost-effective method of nanoimaging.
"Now the question is, how good can we get? Can we get down to single-molecule accuracy? Because in the end, you want to reach a resolution that gets down to the fundamental building blocks of life," Boyden shares in the MIT news release.
While other techniques offer high resolution - such as electron microscopy and super-resolution imaging - the equipment required for these methods is often expensive and not readily available. In expansion microscopy, the method allows high-resolution observation of viruses and other biological samples with the conventional light microscope.
A New Gel for Better Nanoimaging Results
In a previous study, Boyden's lab demonstrated nanoimaging around the range of 20 nanometers, expanding the biological samples twice before imaging. This uses an absorbent polymer-based on sodium polyacrylate, which swells when in contact with water. However, this hydrogel compound is not entirely uniform structurally.
Researchers created a new type of gel to work around this limitation - they called it tetra-gel - which results in a more predictable structure. Combining polyethylene glycol (PEG) molecules with tetrahedral sodium polyacrylates, the resulting compound has a lattice-like structure more uniform compared to the previous hydrogels used.
To demonstrate the nanoimaging capabilities of the new compound, researchers expanded particles of the herpes simplex virus type 1 (HSV-1), which has a "distinctive spherical shape." After expanding the viruses, they then compared the shapes compared to those viewed from electron microscopy. Researchers found that the distortion was lower than previous versions of expansion microscopy, with the new cost-effective technique accurate to around 10 nanometers.
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