A New Microscopy Technique Improves Image Quality in Three-dimensional Cell Models

Physicist Rainer Heintzmann is exploring new approaches in fluorescence microscopy. Together with a team from Osaka University, the Jena-based expert in super-resolution microscopy has developed a method that reduces unwanted background light and makes fine details in cell clusters more clearly visible.

Biological samples often consist of complex, three-dimensional structures. In conventional fluorescence microscopes, light from out-of-focus planes causes images to lose contrast and sharpness. This is particularly problematic in cell clusters or organoids, which serve as realistic models for biological processes.

The new method, selective-plane-activation structured illumination microscopy (SPA-SIM), combines structured illumination with the targeted activation of fluorescent molecules. “By selectively controlling the illumination within the image plane, we can reduce disturbing background light and significantly improve image contrast,” explains Prof. Dr. Rainer Heintzmann from Leibniz IPHT and Jena University.

Sharper Images for ­Complex Cell Models

Existing microscopy techniques already aim to minimize unwanted light components – but SPA-SIM goes a step further. The method uses special fluorescent markers that can only be activated in the focused image plane. This results in sharper images with greater detail.

“Until now, it was difficult to look deep into cell clusters without losing image sharpness,” says Heintzmann. “With our method, we can selectively enhance contrast without unnecessarily stressing the sample.” This could be particularly useful for long-term observations of living cells.

From Image Processing to Materials Research

Heintzmann’s work in image reconstruction feeds into interdisciplinary projects, such as the Collaborative Research Center PolyTarget at Jena University, which focuses on polymer-based drug delivery systems for medicine. High-resolution imaging also plays a central role in the ­Leibniz ScienceCampus InfectoOptics, which develops photonic technologies for infection research.

“If we can analyze materials more precisely at the molecular level, this helps not only in cell biology but also in materials research,” explains Heintzmann. The further development of SPA-SIM could thus open up new perspectives in other scientific fields as well.

Original publication: https://doi.org/10.1038/s41592-024-02236-3