The Ion Inquisition
As the co-developer and champion of SOLiD sequencing, what got Kevin McKernan and his colleagues so enthused about Ion Torrent? What got us excited was the potential to break the diffraction limit, says McKernan.
What is the diffraction limit? It is difficult to optically resolve two features that are shorter than the wavelength of light used to measure them. Most DNA measurement systems use light wavelengths of 500-700 nanometers (because smaller wavelengths mutate DNA). But measuring closely packed DNA features smaller than 700 nm makes the two features blur together. In DNA sequencing, the beads need to be spaced 700 nm apart so the photon wavelengths can resolve them, which is highly inefficient.
[In 2010] We were in the process of mapping out another version of SOLiD that would have multiple cameras, says McKernan. We always knew that that would eventually hit the diffraction limit, and wed be fighting a brick fight with photons with the other guys [Illumina] who make the same kind of box.
McKernan says the Ion Torrent technology has the potential to read features less than 700 nm. Thats what opened our eyessomething as small as a transistor can get down to 30 nm. Theyre not there today, but it has a very long runway. Whereas we felt that if we built this next [SOLiD] optical system with multiple cameras and so on, that would probably be the end of the road We were all racing to that endpointeven though it would be a few years outand then what? Nanopores break diffraction limits but there are complications.
On the other hand, the Ion platform not only breaks diffraction limits but also uses the same front end methods as SOLiD. The Ion Torrent platform also features a very different cycle timewhat McKernan calls real time detection on nucleotide incorporation. Taken together, it is easy to see why McKernan and colleagues took the plunge.
Taking McKernans place on the SOLiD team is Michael McKenna, who formerly worked for Rothberg at Curagen, working on its own DNA ultra-thin gel sequencer. He seemed like the perfect fit to shepherd this along, says McKernan. But he deflected inquiries about Life Technologies other NGS program, a single-molecule sequencing system under the direction of Joseph Beecham that has been dubbed StarLite.
I was always focused on SOLiD, he says diplomatically. It was very exciting work, I love Joes work. Its fascinatingtheres nothing cooler than watching single molecules in real time. K.D.