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Near-isotropic super-resolution microscopy with axial interference speckle illumination
Hajun Yoo1, Kwanhwi Ko1, Sukhyeon Ka1
1School of Electrical and Electronic Engineering, Yonsei University, Seoul, Korea.
Nature Communications
|October 20, 2025
Summary
Axial interference speckle illumination-engineered structured illumination microscopy (AXIS-SIM) enhances axial resolution in super-resolution imaging. This minimal-modification technique achieves isotropic super-resolution without complex optics, improving biological specimen visualization.
Area of Science:
- Biophysics
- Optical Microscopy
- Super-resolution Imaging
Background:
- Super-resolution microscopy advances biological imaging but struggles with isotropic resolution across all dimensions.
- Achieving high axial resolution often requires complex and sensitive optical setups.
Purpose of the Study:
- Introduce axial interference speckle illumination-engineered structured illumination microscopy (AXIS-SIM) for enhanced axial resolution.
- Develop a minimal-modification approach for improved 3D super-resolution imaging.
Main Methods:
- Utilized constructive interference from a back-reflecting mirror for axial resolution enhancement.
- Implemented AXIS-SIM without additional phase control or complex beam shaping.
- Achieved lateral and axial resolutions of 108.5 nm and 140.1 nm, respectively.
Main Results:
- AXIS-SIM demonstrated superior optical sectioning and improved axial resolution beyond conventional 3D-SIM.
- The method showed robustness against alignment errors and sample-induced aberrations.
- Enabled high-throughput 3D super-resolution imaging of diverse biological specimens.
Conclusions:
- AXIS-SIM offers a simplified yet effective approach to achieving isotropic super-resolution.
- The technique visualizes 3D cell morphology, nanoscale distributions (lysosomes, microtubules), and lysosomal dynamics with enhanced axial clarity.
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