Key facts at a glance:
- The new method achieves a spatial resolution of 156 nanometers and can capture rapid processes in living cells.
- It combines super-resolution microscopy with fluorescence lifetime measurements, providing additional information about cells.
- The technique could help researchers investigate the effects and side effects of drugs in greater detail.
“By combining super-resolution with fluorescence lifetime measurements, we can not only see where certain molecules are located within a cell. We also gain information about the molecular environment in which they are located,” says Dr. Henning Ortkraß, one of the authors of the study and a member of the
research group led by
CHEM-SCAN project coordinator Professor Thomas Huser.
Seeing more when drugs affect cells
The researchers combine two techniques: Structured illumination microscopy (SIM) makes cellular structures visible that are too small to be resolved by conventional light microscopes. Fluorescence lifetime imaging microscopy (FLIM), meanwhile, measures how long fluorescent molecules emit light. This lifetime can change depending on their molecular environment, for example due to changes in pH.
Until now, it has only been possible to combine this information to a limited extent with high-resolution microscopy. The new FLIM-SIM technique now combines high spatial resolution, fast imaging rates and a large field of view. The researchers demonstrated these capabilities using a human bone cancer cell line.
A basis for improved drug research
The method is being applied as part of the CHEM-SCAN project, which is funded by the European Innovation Council. Among other things, the project is investigating how chemotherapeutic agents used in cancer treatment can be adapted to act as effectively as possible on both tumours and the metastases that arise from them. To investigate efficacy, specialised fluorescent dyes are used which, with the aid of FLIM measurements, provide information on the state of cancer cells.
The better researchers can observe what drugs trigger inside individual cells, the more precisely they can investigate their effects and potential harmful effects. The new microscopy technique could therefore help improve our understanding of how drugs act at the cellular level and provide a basis for new approaches in biomedical research.
Professor Dr. Thomas Huser on the significance of the research:
“Our results open up a new dimension of contrast for super-resolution microscopy. We can investigate the fine structure of cells at high speed while simultaneously obtaining information about their molecular environment. This provides an important basis for future applications in live-cell and drug research.”