One of this week's GenomeWeb items mentioned an extension of the research agreement between ZS Genetics and the University of New Hampshire. I've heard their head honcho speak a couple of times, and ZS Genetics should be interesting to watch. They propose to (nearly) directly sequencing DNA using electron microscopy. Because DNA, like most organic materials, isn't very opaque to electrons they have a proprietary labeling scheme to label the DNA in a nucleotide-specific manner. Electron microscopy is essentially monochromatic, but if I remember correctly the concept is to grey-scale code the various nucleotides.
One attraction of this sort of scheme is a vision of very, very long read lengths -- the ZS Genetics talks mention 20Kb or so. Such long reads have all sorts of enticing applications, from reading through very complex repeat structures to directly reading out long haplotypes.
The devil, of course, is actually doing this. The data I've seen so far suggests that this approach is definitely in the next-next gen category, along with various other imaging schemes, microcantilevers & nanopores. ZS recognizes that they have a ways to go & propose near-term applications in single-cell gene expression analysis. The danger is that they end up stalled there or worse.
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