Abstract
An important milestone in electron microscopy was the first visualization of single atoms in 1970 with the STEM designed by Albert Crewe. This achievement inspired thoughts that single heavy atoms could be used as super high resolution labels of biological structures by, for example, covalently reacting a heavy atom reagent at the active site of an enzyme. Further investigation of heavy atoms on thin carbon films revealed that they hopped about and that this was not solely thermal motion, but beam induced, since cooling the specimen had little effect. Attempts were made to try various heavy atom compounds but alas, these all behaved similarly, with about 10% of the atoms moving 3-10 Å on successive scans. A gallant effort by M. Beer to sequence DNA using heavy atom base specific labels befell similar problems where the motion of the label prevented high resolution coordinates from being measured.
Published Version
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