Aug 3, 2010
Nanopore barcode scans hybrid probes on DNA
There has been intense interest in recent years in using solid-state nanopores to explore biology, to read out DNA sequences and to perhaps form artificial cells mimicking life. In fact, patents have been issued and companies have been formed around this idea. Yet there is still no DNA being sequenced using these artificial nanopores.
It is not through lack of trying. It is just very difficult. DNAs were evolved to work with proteins, or maybe it's the other way around – this is a separate question for biologists. For physicists, DNA is just a polymer that happens to carry the code of life. They firmly believe that there is no fundamental (physics) reason why DNA sequences cannot be read electronically using a nanopore.
Reporting their results in the journal Full detailsNanotechnology, researchers from Brown University led by physicist Xinsheng Sean Ling have revealed the progress that they have made in using a solid-state nanopore as a barcode scanner for reading out 12-mer "hybridization probes" on a DNA molecule. Since the exact sequences of the 12-mer "probes" are predetermined, it is not a big exaggeration to claim that they have sequenced a DNA, even though it is a very short one, 24 bases in total.
The Ling team has used synthetic oligonucleotides to make a model DNA consisting of three single-stranded DNA molecules (ssDNA). The three ssDNAs have matched ends and are hybridized together to form a single DNA comprising three single-stranded regions separated by two double-stranded segments, each of which is made of 12 bases. When this DNA molecule is pushed through a solid-state nanopore, two distinct dips in ionic current traces appear. Ling believes that this could be the first time that scientists have seen any sequence information from a nanopore experiment.
In principle, it should be possible to design a library of oligos and use nanopores to scan them to obtain DNA sequences. So has the Ling team won the race for nanopore DNA sequencing? Not yet. A quick calculation will show why. At each base, there are four possibilities A, C, G, T. To construct a library of 12-mer oligos, it will be necessary to scan through all 412=16777216 possible oligo probes. In other words, to completely sequence each DNA, more than 16 million samples have to be analysed.
The race is still on.
About the author
Xinsheng Sean Ling is a physicist based at Brown University, US.