Researchers have turned to the AFM, an instrument ideally suited to imaging nonconductive samples, and have now mastered the technique of imaging DNA with it. UC Berkeley biophysics graduate student Matthew Murray can image DNA routinely but, so far, not at a resolution where individual nucleotides can be discriminated. Segments composed of 353 and 701 base pairs of nucleotides have been marked with a protein and imaged. Murray points out two important advantages to using the AFM for mapping. Compared to alternative techniques, such as gel electrophoresis, very little DNA is required, and the AFM is faster, producing an image in one minute as opposed to one hour.
Several obstacles stand in the way.
Segments of DNA that consist of less than 1000 pairs of nucleotides are relatively straight. But longer strands bind up into a tangled pile, much like snarled fishing line. Tangled DNA cannot be measured nor can the interior realm of the tangle be imaged. On the other hand, the distance between one nucleotide and another is about three angstroms, and the AFM can image details as small as one angstrom. Murray says that if a method can be devised to prevent longer strands of DNA from tangling, biologists will want to reassess the feasibility of using the AFM for sequencing.