Single-molecule, single-base-resolution

Single-molecule, single-base-resolution DNA sequencing has been demonstrated. Decoding single-molecule DNA strands is intrinsically difficult because of the high linear data-storage density: The base molecules are only about 3.4 Å apart. Now, a group at Caltech has used a DNA polymerase enzyme to add complementary base units, one at a time, to a single strand of DNA. The base molecules being added were fluorescently labeled beforehand, so the newest member of the DNA sequence at each stage could be observed as it fluoresced. The scientists minimized background noise through careful use of two laser pulses: one to produce pinpoint fluorescence and the other to null or “bleach” the fluorescence to prepare for the next base incorporation. Thus far, sequences of up to six bases have been read. Stephen Quake believes that, within about two years, his group’s process should be a factor of ten faster than standard gel-electrophoresis techniques currently used to sequence DNA molecules, and several orders of magnitude cheaper. (I. Braslavsky et al., Proc. Natl. Acad. Sci. USA 100 , 3960, 2003 http://dx.doi.org/10.1073/pnas.0230489100 .)