膨胀显微镜改变了我们观察细胞世界的方式。
Expansion Microscopy Has Transformed How We See the Cellular World

原始链接: https://www.quantamagazine.org/expansion-microscopy-has-transformed-how-we-see-the-cellular-world-20260204/

## 膨胀显微镜:成像领域的革命 科学家们正在通过一种名为膨胀显微镜的简单技术克服传统显微镜的局限性。该方法于2015年开发,它使用一种水凝胶(与尿布中发现的吸水聚合物相同)来物理膨胀生物样本。 通过将样本浸入这种凝胶中并加水,研究人员可以使材料膨胀,从而有效地放大结构,*而无需*昂贵的高倍显微镜。这使得即使在难以着色的坚硬细胞壁内,也能更清晰地观察到微小的细节。 像Omaya Dudin和Gautam Dey这样的研究人员发现,膨胀显微镜显著提高了图像清晰度和染料渗透性,从而能够研究以前未曾见过的细胞结构。其经济性和易用性正在“普及显微镜技术”,使全球实验室即使使用基本设备也能获得先进的成像技术。这项创新有望加速细胞生物学领域的发现。

## 膨胀显微镜推进细胞成像 一篇最近的《Quanta Magazine》文章重点介绍了**膨胀显微镜**,这是一种通过物理放大生物样本来克服传统显微镜限制的突破性技术。这使得研究人员能够使用标准光学显微镜以前所未有的细节观察细胞结构。 Hacker News上的讨论表明,该技术正被积极应用于雄心勃勃的项目,例如**神经元连接组学**——绘制大脑中完整的神经连接图。**E11 Bio**实验室正在通过在膨胀*之前*用独特颜色遗传标记单个神经元,然后在放大的样本中追踪它们来开创这项技术。 E11 Bio最近发布了其工作的大型数据集,展示了该技术的“大数据”应用,并使其公开可用。这种方法提供了一种强大且日益普及的方式来探索细胞世界的复杂性。
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原文

When you slip a slide under a microscope, a system of glass lenses magnifies the object of your attention — a microbe, for example. But even with the largest zoom on a classic compound optical system, scientists struggle to make sense of finer details, which can be further obscured when tough cell walls make it difficult to inject dyes that help identify structures.

Now, rather than invest in more powerful and more expensive technologies, some scientists are using an alternative technique called expansion microscopy, which inflates the subject using the same moisture-absorbing material found in diapers.

“It’s cheap, it’s easy to learn, and indeed, on a cheap microscope, it gives you better images,” said Omaya Dudin, a cell biologist at the University of Geneva who studies multicellularity.

Expansion microscopy was developed by Ed Boyden at the McGovern Institute for Brain Research at the Massachusetts Institute of Technology in 2015. Boyden and colleagues successfully expanded a biological sample by infusing it with a hydrogel made of sodium acrylate. A key ingredient layered in diapers to keep babies dry, the compound can absorb hundreds of times its weight in water while retaining its overall structure.

In expansion microscopy, specific biomolecules such as proteins are anchored to the gel. As the gel absorbs added water, its weblike matrix swells, and the space between the web’s anchor points dilates. Ideally, the overall structure remains, allowing researchers to visualize extra-tiny anatomy or see inside cells with tough barriers.

Dudin had spent six frustrating years trying to force antibodies through his target cells’ sturdy walls to bind to specific proteins and visualize their internal structures, and he was only able to do so through a complex freeze-and-thaw protocol that destroyed most of the final product. Desperate, he struck up a Covid-era collaboration with the lab next door that was using expansion microscopy.

“That moment was just magical. All the cells were expanded, everything stained, we could see,” Dudin said. “It very rapidly became clear that we should aim for the sky with this one.”

Gautam Dey, a cell biologist at the European Molecular Biology Laboratory in Heidelberg who studies mitosis, found that the method worked just as well in his lab. The samples were clearer, and the dyes and antibodies penetrated cells more effectively, so the two labs struck up a collaboration to visualize species they had never studied before. They are working to chart the landscape of cytoskeletal diversity, visualizing complex cytoskeletal structures that have never been seen in such detail.

Perhaps most importantly, expansion microscopy is possible for any lab with a basic microscope and the hydrogel. “People have talked about democratizing microscopy before. This is it, it’s happening,” Dey said. “I think it’s just a matter of time before any cell biology lab in the world is doing it. A basic fluorescence microscope is never too far away.”

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