Sophia Zhao

The Yale School of Medicine recently recruited C. Shan Xu and Song Pang, two scientists pioneering an imaging technology that has supported advancements in tissue biology, cell biology and the system of neural pathways in the brain.

Focused ion beam scanning electron microscopy, or FIB-SEM, is a scientific instrument that resembles a scanning electron microscope, or SEM. It is an important imaging technology, allowing for more images to be scanned than before, and can produce higher quality 3D pictures with increased reliability. Xu, director of FIB-SEM Technologies at the Janelia Research Campus of Howard Hughes Medical Institute, and Pang, a research application scientist in the FIB-SEM Technology Division, will join the faculty in the Department of Cellular and Molecular Physiology. Pang will lead collaborations using this technology via a pre-established FIB-SEM Collaboration Consortium Core.

“We can combine this cutting-edge, state-of-the-art technology with Yale’s world class scientists who can utilize it to enable their amazing discoveries,” Xu said.

According to Pang, their goal is to “cultivate a rich ecosystem from image to data analysis to discovery.”

FIB-SEM was most recently used to generate a map of every synaptic connection of a fruit fly brain, but also possesses a wider range of capabilities. In the past, Yale investigators James Rothman and Pietro De Camilli have used the technology to explore the structure of the Golgi complex and contacts between subcellular organelles in neurons, respectively. 

However, there are drawbacks to the technology. Michael Caplan, chair and professor of cellular and molecular physiology, detailed FIB-SEM’s main limitations, emphasizing both the scale allowed and the volume of data generated. 

“One of the challenges for FIB-SEM is the [sheer] mass of the data that is generated. Even a relatively small block of tissue can produce tens of thousands of images,” Caplan wrote. “In order to be useful it is necessary that these images each be analyzed and the structures within them need to be identified and annotated. This process, which is called segmentation, requires the development of artificial intelligence-based image analysis tools. It is hoped that the Yale FIB-SEM program will spark new collaborations with Yale researchers who will help to develop new tools.”

Caplan added that Xu and Pang’s recruitment represents the University’s major commitment to the development of the next generation of FIB-SEM technology and a dedicated effort to make sure that this powerful technique is widely available to the biological science community at Yale. 

According to Caplan, the University has planted the seeds for future collaborations that will influence the directions in which FIB-SEM technology will grow and the capabilities that it will acquire. Furthermore, the availability of a FIB-SEM Collaboration Consortium Core will catalyze discovery across all of the biological disciplines represented at the School of Medicine, the main campus and on West Campus.

“Recruitment of Xu and Pang — prominent scientists in the field will not only bring biological FIB-SEM at Yale to the higher level, it may also boost the usage of other electron microscopies on campus, such as traditional biological electron microscopy and cryo electron microscopy,” Xinran Liu, director of the Center for Cellular and Molecular Imaging Electron Microscopy Facility, wrote in an email to the News. 

In the future, the development of the FIB-SEM program is likely to lead to improvements in this technique’s resolution and in the image processing tools required to analyze the data it generates.

Caplan said that he hopes the development that will be undertaken at Yale will broaden the capabilities of this technique, especially in pinpointing specific molecules within cells. 

“This advancement would be very significant, as though FIB-SEM currently reveals the structures of cells and tissues in exquisite detail, it does not provide insight into the locations of specific molecular components of cells,” Caplan wrote. “The development that will be undertaken at Yale will endeavor to broaden the palette of this technique in order to allow it to pinpoint specific molecules. This achievement would allow FIB-SEM to truly connect insight into cellular structure with understanding of physiological function.”

In 2018, Yale acquired the only focused ion beam-scanning electron microscope in the region. 

MAI CHEN