Progress toward the application of molecular force spectroscopy to DNA sequencing.

Many recent advances in DNA sequencing have taken advantage of single-molecule techniques using fluorescently labeled oligonucleotides as the principal mode of detection. However, in spite of the successes of fluorescent-based sequencers, avoidance of labeled nucleotides could substantially reduce the costs of sequencing. This article discusses the development of an alternative sequencing method in which unlabeled DNA can be manipulated directly on a massively parallel scale using single-molecule force spectroscopy. We combine a wide-field optical detection technique (evanescent field excitation) with one of two methods of applying force in parallel, magnetic or dielectrophoretic tweezers, to attain near single-base sensitivity in the double-stranded character of DNA. This article will discuss the developments of such a single-molecule force spectroscopy technique as a potential technology for genome sequencing.