Novel Microfluidics Platform Enhances Multiplexed Super-Resolution Microscopy

Understanding how cells organize their internal components and coordinate complex molecular interactions is central to the life sciences. To uncover these processes, scientists need to visualize multiple structures and molecules within the same cell simultaneously and determine how they are arranged and interact. This challenge has driven advances in multiplexed super-resolution microscopy, a powerful imaging technique that reveals cellular details beyond the limits of conventional light microscopy. Yet, existing methods often prove difficult to reproduce, technically demanding, and ill-suited for fragile biological samples. 

An international team led by the University of Göttingen and the University Medical Center Göttingen aimed to address these issues. The researchers developed a specialized microfluidics system that makes multiplexed super-resolution microscopy easier to perform, more reproducible, and available to a wider scientific community. Their findings appeared in ACS Nano.

A major goal in cell biology is to observe many proteins and cellular structures at once to understand how they function together inside living systems. These experiments, however, can be sensitive to even small variations, which affects reproducibility. The new microfluidics platform brings greater stability and precision by automatically managing the injection and removal of solutions in the sample chamber. This replaces manual pipetting with controlled fluid handling that maintains consistent conditions throughout labeling and washing cycles.

“The system we have developed means we can maintain high image quality throughout long imaging cycles,” explains Samrat Basak, joint first author of the study. “By keeping conditions consistent across the different labelling and washing steps, the microfluidics platform allows information from different targets to be directly mapped, making it possible to image proteins, specialized structures and complex interactions within the cell.”  

The technique was tested with human cancer cells, which revealed how protein filaments are organized inside cells. The method was also successfully applied to isolated heart muscle cells from mouse ventricles. “The fragile, specialized muscle cells of the heart are particularly challenging to image,” adds joint first author Kim-Chi Vu, emphasizing that the system prevented damage or detachment during imaging.

The design supports manual and automated operation and can adapt to various imaging setups. “The core idea was to develop a system which is cost-efficient, adaptable, and can be redesigned according to specific imaging needs of complex biological systems,” adds senior author Roman Tsukanov.