Press release: Faster, clearer, deeper 3D imaging

No. 209 - 19.12.2025

Research team optimises microscope with innovative technology to benefit research and medicine

Light sheet microscopy produces impressive 3D images of tissue and entire organs, such as the delicate cochlea in the inner ear or the complex brain of a mouse. A thin layer of light, the light sheet, moves through the sample and generates a three-dimensional image layer by layer. However, larger samples create problems for conventional microscopes: the process is slow and the images blurred. This led researchers in Göttingen to develop a technologically innovative light sheet fluorescence microscopy platform that improves imaging and opens up new opportunities for research and medicine. Detailed scans allow, for example, fine networks of nerves or blood vessels to be examined in greater detail. The research team at the University of Göttingen and the University Medical Center Göttingen (UMG) worked in collaboration with the University of Lübeck as part of the Göttingen Cluster of Excellence “Multiscale Bioimaging: From Molecular Machines to Networks of Excitable Cells” (MBExC). The results were published in Nature Biotechnology.

The system captures fine detail clearly, even at 850 nanometres – about the size of one hundredth of the width of a human hair. It also produces 100 images per second in a sample measuring a cubic centimetre – about the size of a sugar cube. The 3D object does not appear blurred in areas, as it would with existing techniques: instead, high resolution is consistent throughout and in all directions. This is achieved by combining standard components with new features: as the light sheet illuminates the sample, it is constantly readjusted. “Thanks to this innovation, we can capture large, clear tissue samples in three dimensions faster and in greater detail than ever before,” says Professor Jan Huisken at Göttingen University. Samples like this are made transparent by chemical processes known as “clearing” so that light can penetrate deeply and the image made sharper. “Each of these clearing methods changes the tissue in a slightly different way,” explains Huisken. “This influences how strongly the tissue bends the light, which causes problems for many microscopes. Our system, however, delivers sharp 3D images even when the clearing process has changed the sample’s refractive index.”

The system is used, for example, to precisely map the connections between nerve cells in the mouse cochlea. “This 3D representation enabled us to examine the detailed structure of the cochlea at the level of a single cell – whether healthy or affected by disease – thereby gaining new insight into its function,” says MBExC spokesperson Professor Tobias Moser, Director of the Institute for Auditory Neuroscience at the UMG.

“Our platform is compact, robust and easily reproducible, because it is based on accessible components,” says lead author Dr Mostafa Aakhte at Göttingen University who made a significant contribution to the development, construction, and optimization of the microscope for many different samples. “The platform will be of great interest to basic research, as well as in actual clinical practice, for example in diagnostics or planning 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

Images openly licensed via CC BY 4.0: Attribution 4.0 International

Contact:

Professor Jan Huisken

Humboldt Professor for Multiscale Biology

University of Göttingen

Multiscale Bioimaging Cluster of Excellence (MBExC)

Email: jan.huisken@uni-goettingen.de