Researching the Foundations of Life

The problem for researchers studying living cells with fluorescence microscopes is the illumination: the intensities of the laser radiation used are higher than those of the sun by a factor of 1000 or more. This intense illumination can permanently damage living cells.

A significant reduction of this photo damage is achieved with light sheet microscopy: unlike all other microscopes, the laser beam – in the form of a light sheet – is applied only in the area within the focus of the objective lens. While this works well for larger organisms, the laws of optics still prevent the transfer of this technology to cell biology. "We had to rein in the laser in a special way so that light only goes where a researcher wants to look and without unduly damaging cells," explains Kalkbrenner. "So we built on the idea of lattice light sheets from Nobel Prize winner Eric Betzig and took it further."

On top of this, the team had to completely rearrange the objective lenses because the cells grow on the cover slips in culture vessels like Petri dishes or multiwell plates.  One would have to look from below at an angle through the cover glass – an impossible task for a microscope objective, because the distortions that occur prevent any imaging.

So they developed a completely new type of microscope optic based on  adaptive freeform elements  that allows to look through the sample vessels ‒ at an angle and from below ‒ at the cells inside without artefacts.  

The team managed to compensate the smallest deviations in carrier dimensions and sample position. Especially the multiwell plate formats, which are so important for the development of active agents in the high content screening process, are accessible to a light sheet microscope for the first time.

All this has been developed to create an easy-to-use, compact system with high automation potential.