Abbe is dead, long live Acronyms.

I don't know about you dear reader, but my head is spinning these days! Who can keep up with the pace of change in imaging techniques of various sorts? The development of GFP-based probes is the most obvious culprit: once upon a time you could actually read every paper detailing probe construction, now it is impossible. Super-resolution imaging is a distant second, but it is catching up fast. I was at a Cold Spring Harbor conference 3 or 4 years ago on "Imaging Neurons". Stefan Hell was an invited speaker. He had just developed his STED microscope, and was obviously very proud of it. This was his second way to break Abbe famous diffraction limit barrier. The first was his 4-Pi microscope. (Both of these techniques have been commercialized by Leica- STED and 4-Pi used specialised equipment, and seem quite difficult to do.) Stefan always includes in his talks a picture of Abbe's grave stone (above), which has his equation for lateral resolution carved into it. Thus, the barrier had been truly "set in stone".

Another speaker at CSH was Mats Gustafsson, who made breaking the diffraction limit seem almost laughably simple by comparison. Mats gives off the air of an amateur genius who can do miraculous things with string and sealing wax, after having thought about a problem carefully. Now Gutsafsson and collaborators have a paper in this week's Science (6 June 2008) in which they use his moire patterning approach (J. Microscopy (2000) 198:82-87).

In this month's Nature Methods there are two further contributions to this field. One is a form of photoswitching of fluorescence (PALM), allowing controids of emission to be defined. The other is by Stefan Hell which localizes the emitted light by stimulated depletion of the excited state (STED). Together, these 3 papers have all the leading references to the work in this new and exciting field.

Subdiffraction multicolor imaging of the nuclear periphery with 3D structured illumination microscopy. Science (2008) 320:1332-1336.

Three-dimensional sub–100 nm resolution fluorescence microscopy of thick samples. Nature Methods (2008) 6:527-529.

Spherical nanosized focal spot unravels the interior of cells. Nature Methods (2008) 6:539-544.