Expansion Microscopy: Key things to know

Expansion microscopy, light pattern
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Advances in biology and medicine are not just in the form of new devices or products. Rather, new methodologies are blazing trails, and microscopy techniques are no exception! In a recent article, Wassie et al describes a new optical microscopy technique that they describe as “expansion microscopy.” They discovered that preserved biological specimens could be physically expanded in an isotropic fashion through a chemical process. Expansion microscopy, shortened to “ExM,” enables nanoscale imaging of biological specimens on conventional microscopes, de-crowds biomolecules in support of signal amplification and multiplexed readout chemistries, and makes specimens transparent. Let’s take a closer look!

What is Expansion Microscopy?

For any new imaging technique, there is always a delicate balance of pros and cons. Often times more thorough results come at expense of time and resources. For example, near-field imaging and far-field super-resolution microscopy techniques allow researchers to image single molecules and nanoscale structures, but these methods require expensive equipment and are time consuming. As a result, 3D imaging of extended cells and tissues, such as in cancer research, are often expensive, lengthy projects. However, Wassie et al show that ExM can “isotropically physically magnify a preserved biological specimen by synthesizing throughout such a specimen a network of swellable polyelectrolyte hydrogel, in a dense and even fashion, which in turn can smoothly expand biomolecules or labels away from each other, even in intact tissues like brain circuitry.” As a result, molecules are isotropically separated in space to greater distances and therefore resolvable even by conventional microscopes.

How is it used?

Naturally, better imaging results from standard equipment yields several advantages. Compared to conventional Super-Resolution Microscopy (SRM) methods, ExM excels at 3D imaging of thick specimens. It also significantly reduces the time needed to perform 3D images without adding more equipment to the lab. One notable disadvantage however is that because of the chemical altering needed to make ExM work, live samples cannot be used. However Wassie et al are hopeful that a combination of multiple imaging methods is a bright future and could allow for the imaging of all kinds of specimens from DNA, RNA, proteins, lipids, and more.

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Citation: Wassie AT, Zhao Y, Boyden ES. Expansion microscopy: principles and uses in biological research. Nat Methods. 2019 Jan;16(1):33-41. doi: 10.1038/s41592-018-0219-4. Epub 2018 Dec 20. PMID: 30573813; PMCID: PMC6373868.