13 Jan. Sharper 3D images from inside the body
Light sheet microscopes make tissue and entire organs visible in 3D images, such as the delicate cochlea in the inner ear or the brain of a mouse. A thin plane of light, the light sheet, moves through the prepared sample and generates a three-dimensional image layer by layer. However, conventional devices reach their limits with larger samples: they are slow and produce blurred images.
Part of the research team (from left): Dr. Mostafa Aakhte, Dr. Lennart Roos, Aleyna M. Diniz, and Prof. Jan Huisken.
Image: Tobias Moser
Researchers are now reporting on a technologically innovative platform for light sheet fluorescence microscopes that generates improved images and is expected to open up new perspectives for research and medicine. The platform was developed by a team from the University Göttingen as well as the University Medical Center Göttingen (UMG) together with researchers from the University of Lübeck and as part of the Göttingen Cluster of Excellence ‘Multiscale Bioimaging: From Molecular Machines to Networks of Excitable Cells’ (MBExC).
High resolution at high recording speed
Side view of a mouse brain (top) and detailed images of a blood vessel, made visible using the novel light-sheet fluorescence microscope. Image: Adapted from Aakhte, Mostafa et al., Nature Biotechnology, DOI: 10.1038/s41587-025-02882-8; licensed under CC BY 4.0
According to the researchers, the system resolves details down to 850 nm. It also captures 100 images per second of samples with a volume of one cubic centimeter. The 3D image is to be captured with uniformly high resolution. According to the researchers, this is achieved by combining commercially available components with new features: while the light sheet illuminates the sample, it is constantly readjusted. In addition, targeted corrections reduce optical errors. “Thanks to this innovation, we can capture large, cleared tissue samples in three dimensions faster and in greater detail than ever before,” says Prof. Jan Huisken from the University of Göttingen. The samples are made transparent using chemical processes so that the light can penetrate deeply. “Each clearing method changes the tissue optically in a slightly different way. This affects how strongly the tissue deflects light. Many microscopes have problems with this. But our system delivers sharp 3D images even with changing refractive indices,” says Huisken.
Cellular resolution for medical research and practice
The system was used to precisely map the connections between nerve cells in the cochlea of mice. “This 3D representation enabled us to examine the detailed structure of the cochlea at the single-cell level in both healthy and diseased states, thereby gaining new insights into its function,” explains MBExC spokesperson Prof. Tobias Moser, Director of the Institute of Auditory Neuroscience at UMG.
Light sheet microscope with newly developed platform scanning a cochlea.
Image: Mostafa Aakhte
“Our platform is compact, robust, and easily reproducible because it is based on accessible components,” says Dr. Mostafa Aakhte from the University of Göttingen, who made a decisive contribution to the development and construction of the microscope and to the measurements. „It is not only interesting for basic research. It can also be used in medical practice, for example in diagnostics and in the planning of complicated operations.“
Original publication
[Aakhte, M. et al. Isotropic, aberration-corrected light sheet microscopy for rapid high-resolution imaging of cleared tissue. Nature Biotechnology (2025). DOI: 10.1038/s41587-025-02882-8]
Source: www.uni-goettingen.de