Hybrid TEM/SEM could revolutionise electron microscopy

Electron microscopes have long been indispensable tools in scientific research, but they also face significant limitations. Now researchers at the City University of Hong Kong (CityUHK) are working on a new quantum electron microscope (QEM) that would eliminate interaction between the electron beam and sample, ushering in a new era for electron microscopes.

Transmission electron microscopes (TEMs) and scanning electron microscopes (SEMs) are essential tools in many modern scientific research projects, providing the high-resolution imaging necessary to study the intricate details of various materials. However, the high-energy electron beams that TEMs and SEMs use can cause significant radiation damage to delicate biological samples — and while cryo-transmission electron microscopy (cryo-TEM) can be used to minimise radiation damage by placing proteins in a layer of vitreous ice, this ice layer introduces imaging noise, hampering resolution.

In response to these challenges, Professor Chen Fu-rong and his team at CityUHK used partial key components of a QEM to design a compact hybrid transmission and scanning electron microscope that can operate at room temperature, dubbed the Pulse Electron Hollow Cone Illumination Hybrid TEM/SEM. This innovative system addresses the limitations of existing electron microscopes in several ways.

First, its pulse electron source reduces the radiation damage of soft material samples, which is particularly crucial for biological samples. Second, the hollow cone illumination offers about four times greater image contrast than that of bright-field images in transmission electron mode, enabling more detailed imaging of the samples. The team will also use their previously developed chromatic and spherical aberration (CS/SS) correctors to further improve spatial resolution.

The hybrid TEM/SEM system is also more cost-effective than conventional TEMs and SEMs. Operating at a low voltage range of 15–30 keV, it can perform 3D protein molecule reconstruction and nanomaterial investigation at room temperature, surpassing the capabilities of cryo-EM.

The team demonstrated that the system’s high-resolution imaging capabilities in various applications, including imaging metal contacts on printed circuit boards, nanoparticles and other biological samples, achieved a super-high surface resolution better than 10 nm. It is expected that the microscope will be operated in transmission mode to observe the 3D structure of proteins and molecules, as well as in scanning mode to observe nano-materials and for semiconductor and chip detection.

“Compared to existing desktop SEM systems, our pulse electron hollow cone system offers excellent SEM imaging quality, comparable to that of the best desktop systems,” Chen said. “There are no equivalent electron microscopes in the market that provide the quality of our system. The unique capability of our pulse hollow cone illumination, allowing 3D protein reconstruction via TEM mode, is not available in any existing desktop SEM.”

The team’s project recently secured funding from the Research, Academic and Industry Sectors One-plus (RAISe+) Scheme, launched by Hong Kong’s Innovation and Technology Commission to unleash the potential of local universities in the transformation and commercialisation of their research. With this funding as well as support from an industry partner, the team plans to establish a mass production line for the commercialisation of the new microscopes within three years.

Image caption: Professors Chen Fu-Rong and Hsueh Yu-Chun share their latest development in April 2023: a time-resolved electron microscope integrating both scanning and transmission electron microscope modes in a compact format.