期刊
NANO LETTERS
卷 20, 期 11, 页码 8127-8134出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.0c03159
关键词
Quantitative Phase Imaging (QPI); Off-Axis Digital Holographic Microscopy; Volumetric Imaging; Phase Contrast Agent; Gas Vesicles; Reporter Genes; 3D Particle Tracking
类别
资金
- NSERC
- National Institutes of Health [R01EB018975]
- Packard Fellowship in Science and Engineering
- Pew Scholarship in the Biomedical Sciences
- Heritage Medical Research Institute
- Gordon and Betty Moore Foundation [4038]
- National Science Foundation (NSF) [1828793]
- Jet Propulsion Laboratory (JPL), California Institute of Technology
- National Aeronautics and Space Administration (NASA)
- Direct For Mathematical & Physical Scien
- Division Of Physics [1828793] Funding Source: National Science Foundation
Quantitative phase imaging and digital holographic microscopy have shown great promise for visualizing the motion, structure, and physiology of microorganisms and mammalian cells in three dimensions. However, these imaging techniques currently lack molecular contrast agents analogous to the fluorescent dyes and proteins that have revolutionized fluorescence microscopy. Here we introduce the first genetically encodable phase contrast agents based on gas vesicles. The relatively low index of refraction of the air-filled core of gas vesicles results in optical phase advancement relative to aqueous media, making them a positive phase contrast agent easily distinguished from organelles, dyes, or microminerals. We demonstrate this capability by identifying and tracking the motion of gas vesicles and gas vesicle-expressing bacteria using digital holographic microscopy, and by imaging the uptake of engineered gas vesicles by mammalian cells. These results give phase imaging a biomolecular contrast agent, expanding the capabilities of this powerful technology for three-dimensional biological imaging.
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