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Mapping Absolute DNA Density in Cell Nuclei using Single-molecule Localization Microscopy
Published on: November 11, 2025
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Oblique-plane single-molecule localization microscopy for tissues and small intact animals.
Jeongmin Kim1,2, Michal Wojcik3, Yuan Wang1,2
1NSF Nanoscale Science and Engineering Center, University of California, Berkeley, Berkeley, CA, USA.
Nature Methods
|August 21, 2019
Summary
Single-molecule oblique-plane microscopy (obSTORM) enables deep volumetric super-resolution imaging in intact tissues and small animals. This new method overcomes limitations of standard techniques for biological samples.
Area of Science:
- Biophysics
- Optical Microscopy
- Cell Biology
Background:
- Single-molecule localization microscopy (SMLM) excels in cultured cells but struggles with intact tissues.
- Existing SMLM techniques face challenges in achieving deep, volumetric imaging within complex biological samples.
Purpose of the Study:
- To develop a novel SMLM platform for deep and volumetric imaging of standard tissue samples and small intact animals.
- To overcome the limitations of current SMLM techniques in tissue-scale imaging.
Main Methods:
- Introduction of single-molecule oblique-plane microscopy (obSTORM).
- Utilizing oblique light-sheet illumination to image oblique sections of samples.
- Demonstration of volumetric SMLM at significant depths.
Main Results:
- Achieved super-resolution imaging at depths up to 66 µm.
- Successfully imaged various biological samples including cells, C. elegans gonads, D. melanogaster larval brain, mouse retina and brain sections, and whole stickleback fish.
- Demonstrated the convenience and effectiveness of obSTORM for standard tissue samples.
Conclusions:
- obSTORM provides a deep and volumetric SMLM platform suitable for tissue-scale samples.
- The technique expands the applicability of SMLM to intact organisms and complex tissues.
- obSTORM offers a convenient solution for high-resolution imaging in diverse biological specimens.
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