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Conventional FIB-SEM
Focused ion beam scanning electron microscopy (FIB-SEM) has been used in materials science and the semiconductor industry for decades, with applications in biological imaging emerging since 2006. The conventional systems, however, offer slower imaging speeds and lack of long-term system stability, limiting their acquisition volume to less than 103 µm3.
Enhanced FIB-SEM (eFIB-SEM)
We redesigned the system architecture and transformed FIB-SEM from a conventional system lacking long term reliability to a robust imaging platform with 100% effective reliability. This enhanced FIB-SEM (eFIB-SEM) technology expands the maximum imageable volume by more than five orders of magnitude and achieves the finest isotropic voxel resolution at 4 nm (Xu et al., eLife 2017; US patent 10,600,615; Xu et al., Nature 2021). By combining with super-resolution fluorescence imaging, the CLEM applications unleash the full potential of intracellular organelle identification with labeling insights.
Using the eFIB-SEM platform, we generated the largest and most detailed connectome in 2020, highlighted in Nature & The New York Times. Additionally, we established the first open access, 3D reference library of whole cells and tissues at the finest isotropic resolution, featured in Nature & TheScientist.
By coupling nanoscale isotropic resolution with meso- and macro-scale volumes, the enhanced FIB-SEM pipeline (Pang & Xu, 2023) ushers in a new era of high-resolution large volume electron microscopy to reveal the structure-function relationships in biology. This is demonstrated by over 40 publications since the technology's debut ( Xu et al., 2017), including Nature (Xu et al., 2021; Heinrich et al., 2021; Parlakgül et al., 2022; Obara et al., 2024), Science (Nixon-Abell et al., 2016; Gao et al., 2019; Hoffman et al., 2020; Ritter et al., 2022), and Cell (Ioannou et al., 2019; Weigel et al., 2021; Sheu et al., 2022), and Neuron (Handler et al., 2023), etc., contributing more than 5,000 citations over the past five years.
Beyond enhanced FIB-SEM
Despite how much the enhanced FIB-SEM technology has contributed, the 4-nm isotropic resolution falls short of robust visualization of 3D ultrastructure of sub-10 nm features. My lab aims to transcend the SEM resolution limit that has persisted for 80 years. Such a technology does not currently exist. With success, it will bridge the fields that are currently not connected: structural biology and cell biology, in the context of probing architecture across scales from protein to organelle to cell, within its native tissue environments.
In addition, we contemplate a 3D cryo-FIB-SEM technology that can reliably image a block of vitreously frozen cells or tissues with good contrast and without the need of heavy metal staining, dehydration, and plastic embedding. This streamlined approach will offer the potential to bypass tedious EM sample preparation needed to be individually optimized for large variety of tissues from different species. Most importantly, it allows the volume EM to unveil the fine details of cells and tissues in their native states.
Medical Research Interests
News & Links
News
- September 13, 2023
Researchers Map the 3D Structure of Touch Receptors and Reveal New Mechanism of Touch Detection
- February 23, 2023Source: Connecticut Academy of Science and Engineering
Connecticut Academy of Science and Engineering Elects 35 New Members in 2023
- January 17, 2022
Newly Recruited Scientists Bring Innovative Imaging Technology to YSM
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Cellular & Molecular Physiology
PO Box 208026, 333 Cedar Street
New Haven, CT 06520-8026
United States
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Sterling Hall of Medicine, B-Wing
Academic Office
333 Cedar Street, Ste BE36A
New Haven, CT 06510
Xu Lab
Lab
350 George Street, Ste 146
New Haven, CT 06511