PALM transforms normal fluorescent blur (top) into high-resolution images (middle and bottom).

BETZIG/AAAS

Conventional fluorescent microscopes normally reach their resolution limit at around 200 nm. Now, Eric Betzig (HHMI, Ashburn, VA), Harald Hess (NuQuest Research LLC, La Jolla, CA), and colleagues present a super-resolution microscopy technique capable of localizing individual fluorescent molecules at the 2–25-nm scale.

When two or more fluorescent proteins in a cell are less than 200 nm apart, their separate signals will be indistinguishable by the average fluorescent microscope and will appear as one bright blob. The new technique devised by Betzig et al., called photoactivatable localization microscopy (PALM), gets around this fundamental problem using two main tricks.

The first trick is to isolate molecules by viewing just a few at a time. This technique can be likened to asking a few scattered people in a crowded auditorium to stand up briefly,...

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