Super-resolution label-free volumetric vibrational imaging

Chenxi Qian, Kun Miao, Li-En Lin, Xinhong Chen, Jiajun Du and Lu Wei ()
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Chenxi Qian: California Institute of Technology
Kun Miao: California Institute of Technology
Li-En Lin: California Institute of Technology
Xinhong Chen: California Institute of Technology
Jiajun Du: California Institute of Technology
Lu Wei: California Institute of Technology

Nature Communications, 2021, vol. 12, issue 1, 1-10

Abstract: Abstract Innovations in high-resolution optical imaging have allowed visualization of nanoscale biological structures and connections. However, super-resolution fluorescence techniques, including both optics-oriented and sample-expansion based, are limited in quantification and throughput especially in tissues from photobleaching or quenching of the fluorophores, and low-efficiency or non-uniform delivery of the probes. Here, we report a general sample-expansion vibrational imaging strategy, termed VISTA, for scalable label-free high-resolution interrogations of protein-rich biological structures with resolution down to 78 nm. VISTA achieves decent three-dimensional image quality through optimal retention of endogenous proteins, isotropic sample expansion, and deprivation of scattering lipids. Free from probe-labeling associated issues, VISTA offers unbiased and high-throughput tissue investigations. With correlative VISTA and immunofluorescence, we further validated the imaging specificity of VISTA and trained an image-segmentation model for label-free multi-component and volumetric prediction of nucleus, blood vessels, neuronal cells and dendrites in complex mouse brain tissues. VISTA could hence open new avenues for versatile biomedical studies.

Date: 2021
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DOI: 10.1038/s41467-021-23951-x

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