If you’re familiar with transmission electron microscopy, you probably know that it can capture the microscopic world at the atomic scale with remarkable clarity. But what you may not realize is that for a long time, TEM could only image “static” samples—much like using a camera to take an ID photo of a nail: the image faithfully reflects whatever the nail looks like at that moment. When researchers want to observe what happens when the nail is heated, stretched, or subjected to an electric current, they typically have to rely on two snapshots—one taken before and one after—to infer what occurred in between. This process is somewhat akin to watching a movie but being able to see only the beginning and the end.

In recent years, a technique known as the “in situ sample holder” has gradually transformed this landscape. As the name suggests, an “sample holder” is the slender rod that carries the specimen into the transmission electron microscope. The term “in situ,” derived from the English phrase “in situ,” means under the original conditions and in the native environment. Accordingly, the core function of an in situ sample holder is to apply external stimuli—such as heating, electrical biasing, mechanical stretching, cryogenic cooling, or even the introduction of gases or liquids—directly within the microscope while simultaneously using the electron beam to record the specimen’s dynamic changes in real time. In short, it turns the transmission electron microscope from a static “ultra‑high‑resolution camera” into a video camera capable of capturing “microscopic documentaries.”

What can an in-situ sample holder accomplish in real-world scientific research? Let’s consider a few examples. In materials science, for instance, when a metallic nanowire is stretched, which atoms within the wire undergo slip, and where do cracks first nucleate? If we simply take a snapshot before stretching and another after fracture, all the intermediate details remain hidden. By contrast, an in-situ tensile‑testing sample holder allows researchers to gradually stretch the specimen inside the electron microscope while recording video, enabling them to directly observe dislocation motion and the initiation and propagation of cracks. Another example: when developing new electrode materials, battery researchers are particularly concerned with whether the material will expand or crack during charging and discharging. Traditional approaches require disassembling the battery to examine its final state, whereas an in-situ electrical‑measurement sample holder can be used to construct a miniature battery directly within the TEM, allowing real-time observation of volumetric changes and structural evolution as lithium ions intercalate into the material.

Of course, the capabilities of in‑situ sample holders extend far beyond this. In addition to mechanical and electrical loading, heating functionality is equally important. With the aid of miniature heating chips, researchers can heat samples inside the electron microscope to several hundred or even over a thousand degrees Celsius, while simultaneously observing phase transformations, grain growth, or catalytic reactions at elevated temperatures. Meanwhile, in the low‑temperature regime, cryogenic sample holders cooled by liquid nitrogen enable protective imaging of fragile biological specimens or sensitive materials at temperatures below minus one hundred degrees Celsius. Notably, recent advances have also introduced liquid‑phase and gas‑phase sample holders, which allow researchers to simulate the real‑world conditions of catalytic or electrochemical reactions within the electron microscope, providing direct visualization of morphological changes on catalyst surfaces during the reaction process.

From a scientific research perspective, the value of these technologies lies not only in their ability to “see” but, more importantly, in their capacity to “see accurately.” China‑based ZEPTOOLS Technology has also built up extensive expertise in the field of in‑situ sample holders. Its PicoFemto series encompasses a wide range of functionalities—including probe‑based manipulation, tensile testing, heating, cryogenic cooling, and three‑dimensional reconstruction—and has provided critical hardware support for high‑impact publications by research groups both domestically and internationally. For instance, these instruments have been employed in studies spanning sodium‑ion batteries, potassium‑ion batteries, memristors, and mechanical characterization of two‑dimensional materials. It is worth noting, however, that the true value of any instrument in scientific research ultimately hinges on the depth of the research question and the rigor of the experimental design; no matter how precise the equipment, it remains merely a tool serving the overarching goals of science.

At present, the development of in‑situ sample‑stage technology still faces several objective limitations. For instance, integrating multiple external field‑application modules within the confined space of the sample holder inevitably increases structural complexity, placing higher demands on the electron microscope’s vacuum integrity and imaging stability. Moreover, during experiments, the electron beam itself can induce radiation‑induced damage to the sample; distinguishing whether observed phenomena arise from external stimuli or from beam–sample interactions remains a critical challenge that researchers must address with care. In addition, interface standards vary across different microscope models, and ensuring the versatility of sample holders is an area that requires ongoing optimization for broader practical implementation.

Future technological trends in in situ sample holders are likely to advance along two main axes: “multi‑field coupling” and “higher spatiotemporal resolution.” Multi‑field coupling refers to the simultaneous integration of thermal, electrical, mechanical, optical, and environmental functionalities within a single sample holder, enabling researchers to more accurately replicate the service conditions that materials experience under complex operating scenarios. Meanwhile, with the maturation of aberration‑corrected electron microscopes and ultrafast electron microscopy techniques, in situ experiments hold the promise of achieving concurrent observations at subnanometer spatial resolution and subpicosecond temporal resolution. These advances will deepen our understanding of the dynamic behavior of materials under realistic conditions and provide a more robust foundation for the rational design of new materials.

Perhaps we can describe the role of the in-situ sample holder as follows: it does not alter the transmission electron microscope itself, but rather expands its capabilities, transforming it from a mere “observation tool” into a true “experimental platform.” On this platform, every microscopic dynamic process has the potential to yield new scientific discoveries.