NABsys is building a solid state nanopore single molecule sequencer. However, rather than directly measuring individual bases or modified molecules, this system uses a sequencing-by-hybridization (SBH) approach. Individual strands of DNA are fragmented into roughly 100kb pieces (roughly 1000-fold larger than the fragments read by the ‘short read’ technologies.) These fragments are then hybridized to a particular hexamer probe which will hyb to several locations along the 100kb strand. The partially-hybridized 100kb sequence is threaded through the nanopore which can measure, via electrical conductance changes, where the hybridization events have occurred.
Hybridization patterns from other 100kb strands hybridized with the same hexamer are combined to create a genome-wide probe map. This process is repeated in parallel with all possible hexamers and the resulting probe maps are then combined to generate the complete sequence of the genome. While little has been said about performance metrics, NABsys speculated back in 2009 that they would be able to produce a 25X coverage genome for $100 in less than an hour.
Key Paper: unknown
Projected commercial availability: unknown
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