The hackers teaching old DNA sequencers new tricks

DNA sequencing is any chemical, enzymatic or technological procedure for determining the linear order of nucleotide bases in DNA. Sanger sequencing by replicative synthesis in the presence of dideoxy nucleotide chain terminator monomers has now given way to 'next generation' sequencing by short parallel read technologies. The term often applies to the entire sequence determination pipeline including post-sequencing software analysis.
In a basement storeroom at Stanford University in California, the guts of a dozen DNA sequencers lie exposed - hundreds of thousands of dollars worth of cameras and lasers, optics and fluid controllers, all scavenged from a late-model, next-generation Illumina DNA sequencer called GAIIx. On the floor, the shell of one old instrument sits empty, picked over like a carcass. "I seem like a hoarder," says Stanford biophysicist William Greenleaf.
But over the past 6 years, this collection has fuelled an effort that has engaged about half of Greenleaf's 18-member lab team. Whereas most researchers use DNA sequencers to, well, sequence DNA, Greenleaf's team is one of a small number that has repurposed the devices for an entirely different goal: to study protein and nucleic-acid biochemistry on a massive scale, from macromolecular interactions and RNA folding to enzyme function.
Broadly, the work demonstrates what's possible when scientists look into the guts of their hardware - proof that equipment isn't necessarily without value just because it is old or outdated.
But there's a reason such technology development is called bleeding edge: things often go wrong. Sarah Denny, a biophysicist who graduated from Greenleaf's lab this year, chuckles when asked whether her equipment offers 'plug-and-play' simplicity. "Many times when you did an experiment, something would break and you'd have to figure out how to get it to work again," she says. But given the volume of data she could extract, the reward was worth the pain. In Denny's case, her team gained a better understanding of RNA folding. Such is life in the do-it-yourself trenches.