  With the continued improvement of sequencing technologies, the prospect of
genome-based medicine is now at the forefront of scientific research. To
realize this potential, however, we need a revolutionary sequencing method for
the cost-effective and rapid interrogation of individual genomes. This
capability is likely to be provided by a physical approach to probing DNA at
the single nucleotide level. This is in sharp contrast to current techniques
and instruments which probe, through chemical elongation, electrophoresis, and
optical detection, length differences and terminating bases of strands of DNA.
In this Colloquium we review several physical approaches to DNA detection that
have the potential to deliver fast and low-cost sequencing. Center-fold to
these approaches is the concept of nanochannels or nanopores which allow for
the spatial confinement of DNA molecules. In addition to their possible impact
in medicine and biology, the methods offer ideal test beds to study open
scientific issues and challenges in the relatively unexplored area at the
interface between solids, liquids, and biomolecules at the nanometer length
scale. We emphasize the physics behind these methods and ideas, critically
describe their advantages and drawbacks, and discuss future research
opportunities in this field.
