A nanopore-based approach that can successfully discriminate between all four nucleotide bases in a DNA strand of known sequence is reported in a paper published online this week in Nature Biotechnology. This is the first time that this has been shown and represents a critical step in the quest for a nanopore technology that can sequence strands of DNA of unknown origin.

The use of nanopores for sequencing was proposed more than 20 years ago but it was not clear if this feat would be possible in actuality. Jens Gundlach and colleagues report experimental data showing that individual DNA nucleotides in a complex sequence can be differentiated based on an ionic current that is modulated as the DNA moves through a nanopore in a membrane. The authors find that the ionic current is affected by several nucleotides that are adjacent to the nucleotide passing through the narrowest opening in the nanopore. New algorithms will be required to decode the current measurements to sequence a DNA strand of unknown sequence.