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Updated: Jan 31, 2026

In situ TEM of Biological Assemblies in Liquid
Published on: December 30, 2013
Addressing some of the technical challenges associated with liquid phase S/TEM studies of particle nucleation, growth
Guomin Zhu1, Holger Reiner2, Helmut Cölfen2
1Physical Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352 United States; Department of Materials Science and Engineering, University of Washington, Seattle, WA 98195, United States.
Abstract:
In situ liquid phase scanning/ transmission electron microscopy (LP-S/TEM), enables direct observation of particle formation and evolution in the hydrated liquid state. Though powerful, this technique has significant technical limitations, which need to be carefully addressed in order to obtain reliable quantitative data. In this paper, we highlight several common challenges seen in LP-TEM, including electron-beam induced particle dissolution and motion, particle-membrane adhesion, contamination, and triggering of reactions. We describe our efforts to address these challenges by modifying solution and interface chemistry, maintaining solution flow, performing systematic post in situ analyses on the samples and applying controlled heating.
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