In situ liquid cell transmission electron microscopy (TEM) is a very useful tool for investigating dynamic solid–liquid reactions. However, there are challenges to observe the early stages of spontaneous solid–liquid reactions using a closed-type liquid cell system, the most popular and simple liquid cell system. We propose a graphene encapsulation method to overcome this limitation of closed-type liquid cell TEM. The solid and liquid are separated using graphene to suspend the reaction until the graphene layer is destroyed. Graphene can be decomposed by the high-energy electron beam used in TEM, allowing the reaction to proceed. Fast dissolution of graphene-capped copper nanoparticles in an FeCl3 solution was demonstrated via in situ liquid cell TEM at 300 kV using a cell with closed-type SiNx windows.

In situ transmission electron microscopy (TEM) has become an increasingly important tool for materials characterization. It provides key information on the structural dynamics of a material during transformations and the ability to correlate a material’s structure and properties. With the recent advances in instrumentation, including aberration-corrected optics, sample environment control, the sample stage, and fast and sensitive data acquisition, in situ TEM characterization has become more powerful. In this article, a brief review of the current status and future opportunities of in situ TEM is provided. The article also introduces the six articles in this issue of MRS Bulletin exploring the frontiers of in situ electron microscopy, including liquid and gas environmental TEM, dynamic four-dimensional TEM, studies on nanomechanics and ferroelectric domain switching, and state-of-the-art atomic imaging of light elements (i.e., carbon atoms) and individual defects.

Understanding the fundamental properties of macromolecules has enhanced the development of emerging technologies used to improve biomedical research. Currently, there is a critical need for innovative platforms that can illuminate the function of biomedical reagents in a native environment. To address this need, we have developed an in situ approach to visualize the dynamic behavior of biomedically relevant macromolecules at the nanoscale. Newly designed silicon nitride devices containing integrated “microwells” were used to enclose active macromolecular specimens in liquid for transmission electron microscopy imaging purposes.We were able to successfully examine novel magnetic resonance imaging contrast reagents, micelle suspensions, liposome carrier vehicles, and transcribing viral assemblies. With each specimen tested, the integrated microwells adequately maintained macromolecules in discrete local environments while enabling thin liquid layers to be produced.