膨胀显微镜技术彻底改变了我们观察细胞世界的方式。
内容总结：
新型显微技术突破细胞观测瓶颈：膨胀显微镜让微观世界“纤毫毕现”
传统光学显微镜虽能放大观测对象，却常因细胞壁过厚、染色困难等问题，难以清晰呈现微观结构的精细特征。如今，一项名为“膨胀显微镜”的创新技术正为科学家提供更经济高效的解决方案——通过使用婴儿尿布中的高吸水性材料，将生物样本物理性膨胀，从而在普通显微镜下实现超分辨率成像。
该技术由麻省理工学院博伊登团队于2015年率先开发。其核心原理是将生物样本嵌入聚丙烯酸钠水凝胶中，使特定生物分子锚定于凝胶网络。凝胶吸水膨胀后，分子间距被均匀拉大，原有结构却得以保留，如同将微小细节“等比放大”，使观测者能清晰辨识此前难以观察的细胞内精细构造。
日内瓦大学细胞生物学家奥马亚·杜丁对此深有体会。他曾耗时六年尝试穿透目标细胞的坚韧细胞壁，却屡屡受挫。在与邻实验室合作采用膨胀显微镜技术后，他激动地表示：“那一刻堪称奇迹——所有细胞成功膨胀、染色清晰，我们终于看见了！”欧洲分子生物学实验室的细胞分裂研究者高塔姆·戴也证实，该技术使其样本成像更清晰，染料与抗体渗透效率显著提升。
尤为重要的是，这项技术仅需基础显微镜和常见水凝胶材料即可实现，大幅降低了高分辨率显微研究的门槛。戴评价称：“这真正实现了显微技术的‘平民化’。全球任何细胞生物学实验室都有条件开展相关研究，普通荧光显微镜足以胜任。”目前，多国科研团队正运用该技术探索此前从未清晰呈现的细胞骨架多样性，推动微观生物学研究进入新阶段。
中文翻译：
膨胀显微技术彻底改变了我们观察细胞世界的方式。将载玻片置于显微镜下时，玻璃透镜系统会放大观察对象——例如某个微生物。但即便使用传统复合光学系统的最大倍率，科学家仍难以解析更精微的细节，而当坚韧的细胞壁阻碍染色剂注入时，这些细节会变得更加模糊。
如今，部分科学家不再追求更昂贵的高精尖设备，转而采用一种名为膨胀显微技术的替代方案——利用尿布中常见的吸水材料使观测样本膨胀。
"这项技术成本低廉、易于掌握，即便用普通显微镜也能获得更清晰的图像。"日内瓦大学研究多细胞生物的细胞生物学家奥马亚·杜丁表示。
该技术由麻省理工学院麦戈文脑研究所的埃德·博伊登于2015年首创。博伊登团队通过向生物样本注入聚丙烯酸钠水凝胶，成功实现了样本膨胀。这种尿布中的核心锁水材料能吸收数百倍自重的水分，同时保持整体结构稳定。
在膨胀显微过程中，蛋白质等特定生物分子被锚定在凝胶网络上。当凝胶吸收水分时，其网状基质会膨胀，锚定点之间的空间随之扩展。理想情况下，样本整体结构得以保留，使研究人员能够观察超微解剖结构或穿透坚韧的细胞屏障。
杜丁曾耗费六年时间试图让抗体穿透目标细胞的坚固壁垒，以期标记特定蛋白质并显影内部结构，最终只能通过复杂的冻融方案实现——这导致大部分样本遭到破坏。在疫情时期，他偶然与隔壁使用膨胀显微技术的实验室展开合作。
"那一瞬间堪称奇迹。所有细胞都成功膨胀，染色全面覆盖，我们终于看清了内部结构。"杜丁回忆道，"我们立即意识到这项技术蕴藏着无限可能。"
海德堡欧洲分子生物学实验室研究有丝分裂的细胞生物学家高塔姆·戴伊发现，该方法在他的实验室同样效果显著。样本更清晰，染色剂与抗体穿透效率更高，促使两个实验室携手探索从未研究过的物种。他们正致力于绘制细胞骨架多样性图谱，以前所未有的精细度呈现复杂的细胞骨架结构。
或许最重要的是，任何拥有基础显微镜和水凝胶的实验室都能开展这项研究。"人们常提及显微技术的民主化，现在它正在成为现实。"戴伊指出，"全球细胞生物学实验室普及这项技术只是时间问题。基础荧光显微镜从来都不是遥不可及的设备。"
英文来源：
Expansion Microscopy Has Transformed How We See the Cellular World
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.”