Disruptive technology for biological specimens: How expansion microscopy can reshape medical diagnostics?

With the advancement of technology, new biological imaging technologies are emerging one after another. Among them, "Expansion Microscopy" (ExM), as an innovative sample preparation tool, has attracted widespread attention in the biomedical research community. The core idea of ​​this technology is to enlarge tiny structures in cell or tissue samples through polymer systems, so that they can be captured by a wider range of microscopy techniques. The advent of expansion microscopy breaks the resolution limitations of traditional microscopes, allowing researchers to explore more delicate biological structures at a lower equipment cost.

Expansion microscopy can magnify a sample up to 16 times its original size, allowing researchers to identify small structures with standard equipment.

Technical Principles

The principle of expansion microscopy is based on introducing polymer networks into the sample. The polymer network physically expands in response to chemical reactions, increasing the size of the biological structure. This process effectively avoids the resolution limitations of traditional optical microscopes, especially when detecting tiny structures such as synaptic vesicles, which are only 40-50 nanometers in diameter, and the resolution is only 200 nanometers.

The most important principle is that expansion microscopy does not require specialized equipment and its material costs are almost negligible.

Historical Background

Expansion microscopy was first proposed in 2015. With the continuous advancement of multiple studies and the improvement of technology, it has been applied to the analysis of various biological samples. This technology has continued to develop over the years, especially in the visualization and molecular sequencing of RNA molecules. In 2022, Hendrickson et al. further broke through the limitations of expansion microscopy and developed Expansion-Revealing Microscopy, further expanding its scope of application.

Application Areas

Medical Diagnosis

The changes and potential that expansion microscopy brings to biomedical diagnostics are undoubtedly one of its most striking features. Conventional microscopes are limited in their ability to examine cell structures and biomolecules, but expansion microscopy allows medical researchers to image tissue samples at high resolution without having to rely on high-cost equipment. Recent studies on kidney disease and breast neoplasms have shown that the use of expansion microscopy is very effective for early detection and diagnosis.

Expansion microscopy improves the resolution of optical microscopy, making medical imaging possible.

Neuroscience

In neuroscience research, expansion microscopy is an important tool for revealing the structure of neural circuits. This technology can more clearly map neurons and synapses and locate them at the molecular level, helping to reveal how the nervous system works. For example, by expanding on brain samples, the researchers discovered pathological features of the beta-amyloid protein associated with Alzheimer's disease.

Advantages and Challenges

The main advantage of expansion microscopy is that it does not require expensive optical equipment and can achieve high-resolution images under standard microscopes. However, this technique is also faced with many challenges, including potential failures at various steps in the sample preparation process. For example, if cells are not completely digested, it will affect the uniform expansion of the sample, resulting in image distortion. At the same time, some fluorescent markers tend to fade during the polymerization process, further increasing the difficulty of the experiment.

Although the application potential of expansion microscopy is huge, its specific operation still requires rigorous control.

As the technology continues to improve, the application of expansion microscopy in the biomedical field is rapidly expanding. In the future, could this technology revolutionize our understanding of cells and their functions? What novel applications will emerge in future research?

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