Autobiography Stefan Hell

lenge was to create a main fbcal diffraction peak with negligible secondary ones,
i. e. an optical transfer Function of the microscope that was both expanded and
contiguous along the optic axis. Otherwise, one would end up with artefacts. With
the use of Winfried Denk’s two-photon excitation modality, making contiguous
transfer functions became reliably possible. But there were still no images of bio-
logical specimens taken and, of course, using two opposing lenses didn’t break the
diffraction barrier. The latter particularly vexed me. However, the good thing was
that the resolution question in far-field microscopy had been raised for all to see,
and I had a foot in the door.
Ernst Stelzer and I ended up with very different views on how realistic it
would be to overcome the diffraction limit. We parted ways in 1993. He went on
to tilt two lenses so that they were at almost 90° to each other and called it confocal
theta microscopy. Later he refined this arrangement into what is now called the
light sheet microscope, an increasingly populär microscopy modality.
In the spring of 1993, the stipend ran out, and I could no longer stay at the
EMBL. The DFG, which had just set up a special funding program called ‘New
Microscopy for Biology and Medicine’, told me that I couldn,t apply for research
funds because I had no job and no laboratory to work in. They funded a couple
of near-field projects, though. But once again I was lucky: Also working in the
Stelzer group was a Finnish colleague, Pekka Hänninen, who planned to return to
Finland. Pekka had realised the timeliness of the resolution topic and introduced
me to his future professor, Erkki Soini of the University of Turku, who offered
to submit a research proposal on 4Pi microscopy to the Academy of Finland. The
Academy agreed, on condition that I worked in Turku. So I arrived in Turku in
the summer of 1993, and Erkki Soini, Pekka, and I worked very hard to set up a
small optics laboratory. We started where I had left off at the EMBL, namely with
4Pi microscopy - firstly, because it was the only tangible approach at the time, and
secondly because the credibility of the whole endeavour was at stäke. Rumour
was that it will end up like all other ‘superresolution’ efforts before, namely as an
academic curiosity.
At the same time, I feit that simply changing the way light is focused will
not change matters fundamentally. The only way to do so would be either via
some quantum optical effects or - what appeared more promising - via the States
of the molecules to be imaged. The molecules whose States could be most easily
played with were fluorescent ones, which were also those of interest in the life
Sciences.
On a Saturday morning in the fall of 1993 I was browsing through Rodney
Loudon’s book on the quantum theory of light in the hope of fmding something
suitable. A few weeks earlier I had imagined what would happen if the fluorescent
molecules would be re-excited from the excited state using slightly offset beams.
When my eyes caught the chapter about stimulated emission, it dawned on me:
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