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Cryo-CLEM, Cryo-FIB, and Cryo-ET
The advanced cryoelectron tomography (cryo-ET) system at Yale includes a cryo-CLEM, cryo-FIB/SEM, and 300KV Krios TEM.

Advancing Interdisciplinary Research

Yale’s outstanding cryo-ET infrastructure and strong record of impactful cryo-ET research greatly impact the breadth of research in the Liu lab and across campus. We combine cryo-ET, cryo-EM, and cryo-FIB to address longstanding and essential questions in modern biology – as well as to advance highly interdisciplinary work. Our cryo-ET workflow has enabled a remarkable array of discoveries in structural biology, microbiology, cell biology, and neuroscience.

As part of Yale’s rapidly growing and diversifying cryo-FIB/EM/ET community as well as the Microbial Sciences Institute, the Liu lab is committed to exploring new sample preparation techniques as soon as they become available. We regularly collaborate to share our expertise in advanced applications of cryo-FIB/ET with colleagues across many academic departments at regional symposia, workshops, journal clubs, and in the lab. Overall, we hope to continue building a stronger cryo-EM/ET community for the development and dissemination of state-of-the-art methods relevant to various scientific fields.

Cryo-FIB/EM/ET Applications

As these cutting-edge techniques are rapidly evolving, training is central to the development of the next generation of scientists. Yale offers an array of cryo-EM/ET training programs and to continue building cross-disciplinary bridges among biologists, physicists, and computer scientists.

Faculty, students, and postdocs may contact the Liu lab to learn more about cryo-FIB/fLM instruments and potential applications to advance their research projects. Many members of our lab have been trained to operate cryo-FIB/fLM instruments, resulting in multiple publications (e.g., Huang et al., Nature 2021; Xiang et al., Cell 2021). Comprehensive and systematic training on cryo-FIB includes system preparation, grid loading, target selection, rough milling, final polishing, and grid unloading and storing. This FIB/SEM system supports many interdisciplinary projects across campus.

The following diverse projects highlight junior scientists, including students and postdocs, involved in cryo-FIB operation:

Visualization of Legionella pneumophila using cryo-FIB and cryo-ET.
  • bacterial secretion systems - Shuaiqi (Phil) Guo and Shoichi Tachiyama, Liu lab
Visualization of Pseudomonas aeruginosa using cryo-Em, Krios, and FIB.
  • VPS13C and lipid transport - Shujun Cai, De Camilli lab
  • mechanismof host defense - Shiwei Zhu, MacMicking lab
  • replication of RNA viruses - Benjamin Götte, Pyle lab
  • HIV-host interaction - Wei Zheng and Shuai Yuan, Xiong lab
  • nuclear envelope sealing mechanisms - Nick Ader, King and Lusk labs.


Understanding living systems at the molecular level

The Aquilos™ Cryo-FIB is the first cryo-DualBeam™ (focused ion beam/scanning electron microscope) system dedicated to preparation of frozen, thin lamella samples from biological specimens for high-resolution tomographic imaging in a cryo-transmission electron microscope (cryo-TEM). Since Yale Aquilos was installed in April 2019 - as well as upgraded in December 2021 - we have prepared over ten different kinds of lamella samples, including bacterial, cell, and biofilm samples (Yeast, E. coli, Salmonella, F. novicida, Cos 7, Bacillus, Neutrophil, Chlorella, P gingivalis and Treponema denticola co-biofilm, et al). The Liu Lab welcomes research collaborations. Please contact Jennifer Aronson with any inquiries.

Yale Cryo-FIB Aquilos Protocol 1

Yale Cryo-FIB Aquilos Protocol 3