The miracle of expansion microscopy: How to make cells bigger and clearer?

In the context of the rapid development of biological science today, expansion microscopy (ExM) has become an emerging technology, providing unprecedented opportunities for studying cellular and molecular structures. The core of this technology is to magnify biological samples through water expansion, so that tiny biological structures can be clearly observed even under an ordinary optical microscope, thereby reducing dependence on high-performance microscope equipment.

Principle

The basic principle of expansion microscopy is to introduce a polymer network into a sample and then use a chemical reaction to physically expand the network, thereby increasing the size of the sample. This process not only improves image resolution, but also enables staining of specific molecules or proteins to further analyze their distribution in cells. Unlike conventional electron microscopy, ExM does not require expensive equipment, making the study of tiny structures accessible to more and more researchers.

Steps

Expansion microscopy involves multiple steps, mainly including staining, linkage, digestion, and expansion. The success of these steps directly affects the clarity of the final result. First, researchers need to stain the sample to ensure that the fluorescent marker used can be linked to the subsequent polymer. Next, a polymer gel is linked to the cells, into which the fluorescent markers are fixed. Care must be taken during the digestion step to prevent the sample from expanding evenly during expansion. Finally, the overall expansion of the sample allows the linked fluorescent markers to be amplified, achieving higher resolution.

Historical Background

Expansion microscopy technology was first proposed by Fei Chen, Paul W. Tillberg and Edward Boyden from MIT in 2015. Since then, the application scope of ExM has gradually expanded. Over time, researchers have sought to improve upon this technology to address its traditional limitations with labeled probes and to introduce more applications for biological samples.

"The emergence of expansion microscopy provides researchers in the biomedical field with new analytical tools, making nanoscale biological structures no longer an unattainable dream."

Application Areas

Expansion microscopy is widely used in biomedical research, especially in disease diagnosis, neuroscience and other fields. Previously, many cell structure examinations relied on traditional diffraction-limited microscopy techniques. However, with the help of ExM, researchers can examine key biomolecules within cells at higher resolution, advancing the development of disease pathology.

Advantages and limitations

A major advantage of expansion microscopy is that it does not require expensive electron microscopy equipment. This is undoubtedly good news for many research institutions with limited funds. However, this technique is not without flaws; mistakes in any of the preparation steps can result in distorted images or cell damage. In addition, the deactivation problem of fluorescent labels also limits the wide application of ExM.

Future Outlook

Expansion microscopy technology is still under development and may achieve greater breakthroughs in fields such as pathology, clinical diagnosis, and neuroscience in the future. As technology continues to improve, scientists are expected to discover more sophisticated biological structures to assist in the development and treatment of diseases. In this case, will there be more mysteries of the microscopic world waiting for us to explore?

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