The 'strand sequencing' method encompasses the identification of individual DNA bases on a single-stranded DNA molecule.  As the strand passes through the nanopore, an ionic current through the pore is modulated. This signal provides information about the identity of the bases inside the pore.

Oxford Nanopore is developing strand sequencing technology using the same core hardware that is used for exonuclease sequencing and protein analysis.  A protein nanopore/enzyme complex for strand sequencing can be deployed using the Company's proprietary array chip and reader system.  This project is being progressed through internal R&D and projects with our collaborators in leading nanopore academic laboratories.

To recall, nanopore sensing works by measuring a current passing through a nanopore.  As molecules pass through the nanopore, the current is modulated and molecules may be identified by the characteristics of that modulation.

One requirement of strand sequencing is to identify correctly the individual DNA bases as they pass through the pore.  In a nanopore made from the protein alpha hemolysin, if a DNA strand is passed through the pore then 10-15 nucleotides may span the inside of the nanopore at any one time.  A successful method of DNA sequencing must discriminate the identity and sequence of individual bases within this strand.  

Oxford Nanopore and collaborators are developing methods to improve the power to discriminate bases, including the use of one or more constriction points in the nanopore combined with powerful methods of signal analysis.  A recent publication from Professor Hagan Bayley's laboratory can be found here; 'Multiple base recognition sites in a biological nanopore: two heads are better than one'.  Further publications can be found here. 

In addition, translocation of the DNA strand through the nanopore must be controlled; if driven electropheretically, DNA passes through the nanopore too quickly for accurate base-resolution measurement with current systems.  Oxford Nanopore and our collaborators are developing methods of combining molecular motors such as processive enzymes to control the rate at which the DNA strand passes through the nanopore.  A 2010 review of published work in this area, by Oxford Nanopore collaborator Professor David Deamer, may be found here.

Oxford Nanopore has a broad IP portfolio encompassing the use of nanopores for DNA sequencing and other applications. For more information click here.