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Preparation of Samples for Electron Microscopy01:20

Preparation of Samples for Electron Microscopy

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To be visualized by an electron microscope, either transmission or scanning, biological samples need to be fixed (stabilized) so the electron beam does not destroy them and dried thoroughly (desiccated/dehydrated) so the vacuum does not affect them. Fixation needs to be done as quickly as possible because the sample properties will start changing as soon as it is removed from its natural environment. For example, in a tissue sample, the oxygen levels begin decreasing, causing an altered...
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Updated: Sep 17, 2025

Studying Dynamic Processes of Nano-sized Objects in Liquid using Scanning Transmission Electron Microscopy
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启用液体扫描电子显微镜用于使用真空兼容液体囊的治疗悬浮.

Raina Borum1, Paul Reichert2, Zhao Li3

  • 1Analytical Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.

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|July 3, 2025
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概括

我们增强了液体扫描电子显微镜 (湿SEM) 通过改善样本粘附和对比度来成像治疗悬浮. 这允许对小型有机和生物材料进行高分辨率的实地分析,有助于药物开发.

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科学领域:

  • 材料科学 材料科学 材料科学
  • 生物技术是生物技术.
  • 分析化学 分析化学

背景情况:

  • 液体扫描电子显微镜 (湿SEM) 能够在液体环境中对材料进行高分辨率成像.
  • 诸如样品粘附性差,辐射敏感性和低对比度等挑战限制了治疗悬浮液的湿SEM.
  • 现有的方法不足以在原生状态下表征小型有机和生物材料.

研究的目的:

  • 克服湿SEM用于分析治疗悬浮物的局限性.
  • 扩大湿式SEM的应用范围,用于小型有机和生物材料的现场表征.
  • 为了提高成像分辨率和对比度,在悬浮中成像亚微米粒子.

主要方法:

  • 使用真空兼容的液体电池,表面修改成像窗口,以增强样品粘附性.
  • 采用成像间隔器来提高异质颗粒大小的采样效率.
  • 加入了加多酸,通过Z-contrast增强对比度和分辨率.

主要成果:

  • 与未涂层的相比,在表面涂层的成像窗口上显著改善了样品的粘附性.
  • 在悬浮中的亚微米蛋白质颗粒中达到大约10nm的分辨率.
  • 成功阐明了粒子属性细节,这些细节影响了in situ的风湿学和药物动力学行为.

结论:

  • 制定策略来克服湿SEM治疗悬浮的关键局限性.
  • 已建立湿SEM作为一种多功能工具,用于在现场分析有机和生物软材料.
  • 强调高分辨率成像对于促进治疗过程开发和配方设计的重要性.