Abstract

The detection of single atoms in the gas phase was first accomplished in 19771 and the detection of single molecules in a solid matrix at low temperatures in 1989.2 The detection of single chromophore molecules in aqueous solution presents different problems and has only recently been achieved.3 Because of the many applications of ultrasensitive detection in liquid environments, the sensitivity obtained using fluorescence detection has had a long history of incremental improvements. A new urgency came to the field when it was suggested that DNA may be sequenced at rates many times that of current methods by sequential enzymatic cleavage of an appropriately labeled single DNA strand followed by detection and identification of the individual labelled nucleotides.4

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