Tuesday, September 25, 2007

A First Commercial Nanopore Foray?

Today's GenomeWeb carried the news that Sequenom has licensed a bit of nanopore technology with the intent of developing a DNA sequencer with it. The press release teases us with the possibility of sub-kilodollar human genomes.

Nanopores are an approach which has been around for at least a decade-and-a-half -- a postdoc was working on it when I showed up in the Church lab in 1992. The general concept is to observe single nucleic acid molecules traversing through a pore. It's a great concept, but has proven difficult to turn into reality. I'm unaware of a true proof-of-concept publication showing significant sequence reads using nanopores, though I won't claim to have really dug in the literature. Even such an experiment would represent a small step but not an imminent technology -- the first polony sequencing paper was in 1999 and only in the last few years has that approach really been made to work.

Which is one reason I'm a bit apprehensive as to who bought the technology. Sequenom has done interesting things and has a great name (I had independently thought of it before the company formed; if only I had thought to cybersquat!). But, they have had a rough time in the marketplace, and were even threatened with NASDAQ delisting a bit over a year ago. Their stock has climbed from that trough, but they're hardly flush: only $33M in the bank and still burning cash at a furious rate. Can Sequenom really invest what it will take to bring nanopores to an operational state, or will nanopores be stuck with a weak dance partner which steps on its toes? I hope they pull it off, but it's hard to be optimistic.

It would also be nice to learn more about the technology. I found the most recent publication of the group, but it is (alas!) in a non-open access journal (Clinical Chemistry, though oddly Entrez claims it is). I might spring the $15 to read it, but that's not exactly a good habit to get into. The most enticing bit in that the current version apparently relies on generating cleverly-labeled DNA polymers that somehow transfer the original sequence information ("Designed DNA polymers") and then detecting the sequence due to passage through the nanopore activating the labels. It sounds clever, but moves away from the original vision of really, really long read lengths by reading DNA directly through the nanopore. The question then becomes how accurate is that conversion process and what sorts of artifacts does it generate?


Anonymous said...

Hello, and thanxx for sharing your comments on nextgen sequencing.

We are talkink about >$600 but I want to save you $15. Here is what you are missing:

I'm fascinated by this upcoming breakthrough of Nanopores. It was really funny to see the paper of Trepagnier EH, Radenovic A, Sivak D, Geissler P, Liphardt J. (Controlling DNA Capture and Propagation through Artificial Nanopores. PMID: 17705552) who talk about reading speed of the technology. And it goes so fast (30.000 b/ms) that they have to work on how to slow this speed to allow better interpretation. At least this is what I understood from the paper They succeed into reducing the speed to 150 b/ms !!!

i'm using myself CEquencing and we usually achieve 300 bases in 60 min.

Here, with Nanopores, at a reasonable speed of reads, we are talking about 540 megabases in 60 min!!!

Could you imagine that?

Anonymous said...

you will have made the modification, we are talking about $600k instruments...