The preparation of extremely thin samples, which are required for high-resolution electron microscopy, poses extreme risk of damaging biological macromolecules due to interactions with the air-water interface. Although the rapid increase in the number of published structures initially gave little indication that this was a problem, the search for methods that substantially mitigate this hazard is now intensifying. The two main approaches under investigation are (a) immobilizating particles onto structure-friendly support films and (b) reducing the length of time during which such interactions may occur. While there is little possibility of outrunning diffusion to the interface, intentional passivation of the interface may slow the process of adsorption and denaturation. In addition, growing attention is being given to gaining more effective control of the thickness of the sample prior to vitrification. Expected final online publication date for the Annual Review of Biochemistry, Volume 90 is June 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

中文翻译：

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为冷冻电子显微镜准备更好的样品：生化挑战并不仅仅在于分离和纯化。

高分辨率电子显微镜所需的极薄样品的制备由于与空气-水界面的相互作用而具有破坏生物大分子的极大风险。尽管最初发布的结构数量的迅速增加几乎没有迹象表明这是一个问题，但是现在正在寻找能够显着减轻这种危害的方法。正在研究的两种主要方法是（a）将颗粒固定在结构友好的支撑膜上，以及（b）减少可能发生这种相互作用的时间长度。虽然几乎不可能超出扩散到界面的范围，但界面的故意钝化可能会减慢吸附和变性的过程。此外，人们越来越关注在玻璃化之前更有效地控制样品的厚度。《生物化学年度评论》第90卷的最终最终在线发布日期为2021年6月。请参阅http://www.annualreviews.org/page/journal/pubdates以获取修订的估算值。