DNA sequencing (solid state nanopores)

 

 

graphics: right: double stranded DNA has been detected passing through a nanopore in a graphene sheet.  left: nanopores fabricated in synthetic materials such as silicon nitride may provide a low-cost, higly scalable alternative to protein nanopores in lipid bilayers.

 

A future generation of nanopore technology is 'solid-state' nanopores.  These are man-made holes in synthetic materials, for example silicon nitride or graphene. As fabrication methods improve towards the ability to consistently manufacture nano-scale pores in thin materials, there is potential to further improve cost and yield of nanopore sequencing.


In 2008, Oxford Nanopore established a collaboration with the laboratories of Professor Daniel Branton and Professor Jene Golovchenko at Harvard University.  Early pioneers of nanopore sensing, and in particular in the development of methods of solid-state sequencing, Oxford Nanopore supports research in these laboratories and licenses the right to develop nanopore discoveries into a single molecule analysis technology. In 2011, a further collaboration was announcedbetween Harvard and Oxford Nanopore, for the development of graphene as a solid-state nanopore sequencing device.
Graphene is a robust, single atom thick ‘honeycomb’ lattice of carbon with high electrical conductivity. These properties make it an ideal material for high resolution, nanopore-based sequencing of single DNA molecules. 

 

In a landmark 2010 Nature publication (S. Garaj et al, Nature Vol 467,doi:10.1038/nature09379) the Harvard team and collaborators used graphene to separate two chambers containing ionic solutions, and created a hole - a nanopore – in the graphene. The group demonstrated that the graphene nanopore could be used as a trans-electrode, measuring a current flowing through the nanopore between two chambers. The trans-electrode was used to measure variations in the current as a single molecule of DNA was passed through the nanopore. This resulted in a characteristic electrical signal that reflected the size and conformation of the DNA molecule.

 

At one atom thick, graphene is believed to be the thinnest membrane able to separate two liquid compartments from each other. This is an important characteristic for DNA sequencing; a trans-electrode of this thickness would be suitable for the accurate analysis of individual bases on a DNA polymer as it passes through the graphene.