CryoFIB Instrument for Biomedical CryoEM/ET Lamellae Preparation
openOD - NIH Office of the Director
Summary
The California NanoSystems Institute (CNSI) at the University of California, Los Angeles (UCLA), is committed
to pioneering nanobiology and biomedical research. Central to this mission, the Electron Imaging Center for
Nanosystems (EICN), established in 2007, provides cutting-edge cryogenic electron microscopy (cryoEM)
instruments and specialized expertise to elucidate the mechanisms of molecular machinery at the nanometer
scale. A previous NIH S10 award was pivotal in installing the world’s first operational Titan Krios in 2008, a
landmark achievement that fueled the cryoEM revolution of the past decade. This instrument produced data for
one of the earliest near-atomic-resolution single-particle cryoEM structures and played a critical role in
Moderna’s groundbreaking mRNA vaccine development. Building on this success, a second NIH S10 award
enabled the acquisition of a Titan Krios G4 in 2024, equipped with advanced technologies for both cryoEM
imaging and cryogenic electron tomography (cryoET) tilt series acquisition. These state-of-the-art instruments
support hundreds of registered UCLA users, facilitating atomic-level structural analysis of isolated or enriched
biological complexes for a wide range of research applications.
While EICN’s cryoEM and cryoET capabilities meet current user needs, the lack of a cryogenic focused ion
beam (cryoFIB) instrument significantly restricts our large user base from conducting in situ structural studies
within cells and tissues using cryoET. Most cells, exceeding 1 µm in thickness, are too dense for electron
penetration and require precise milling into lamellae of 200 nm or less to enable high-resolution cryoEM or
cryoET imaging. This application seeks funding to acquire an Aquilos 2 cryoFIB instrument, which will
empower NIH-supported biomedical research across 38 user laboratories (including 26 major users) within
EICN’s extensive user community. The proposed cryoFIB will substantially enhance EICN’s cellular cryoET
capabilities, advancing federally funded research in critical areas such as viral and microbial infections,
neurodegenerative disorders, tumorigenesis, therapeutic development, drug design, and vaccine delivery
systems, as well as the PI continuous cryoEM/cryoET method development.
The Aquilos 2 cryoFIB will benefit from robust institutional support, including dedicated staff, ongoing
instrument maintenance, and operational resources, ensuring long-term impact and accessibility. The
instrument will be managed by EICN’s highly experienced core facility team, which has successfully operated
the facility for 18 years since its inception. The principal investigator, managing director, facility technician, and
user coordinator possess the technical expertise and operational experience necessary to ensure the
cryoFIB’s seamless integration and productive use. This high-end S10 instrument will immediately bolster NIH-
funded biomedical research across UCLA’s colleges of natural sciences, engineering, and the David Geffen
School of Medicine, driving transformative discoveries in structural biology and beyond.
Up to $2.0M
health research