Monday, January 31, 2011

Three Visions of The Next Phase of Sequencing

When thinking about the current crop of sequencing instruments, it occurred to me that they can be divided roughly into three categories, representing three different visions of what sequencing will look like for the next few years.

In the first category you have the monster instruments. I will use as my exemplar Pacific Biosciences, though this category would also include Helicos and to some degree the mainline sequencers of the other families. These instruments are large and require their own floor space (or effectively so). Think PDP-11 as an analogy.

In the second category are the "personal sequencers". The archetype is the Ion Torrent Personal Genome Machine (PGM), but with similar form factors are the 454 Jr and MiSeq. These instruments sit atop a bit of bench space. The PGM in particular is meant to be seen: a stylish logo composed of four symbols and even an iPod dock (what next? Personalized "skins" for your PGM?). Think personal computer as an analogy (PGM is a Mac & MiSeq a PC?).

Luke Jostins has a very nice article looking at what Oxford Nanopore has released about their instrumentation. Now, the big catch is that any working chemistry to go with that instrument is still tightly under wraps (and someone from OxNano smothered speculation that any big announcement will come at Marco Island this week). What is striking about their instrument is that while it could theoretically sit on a benchtop, what they are really aiming for are huge gangs of them -- the boxes fit in a standard computer rack. Talk about a data center!

This isn't just a mounting decision; OxNano is thinking in terms of the unique properties nanopores would bring. For example, there wouldn't be set cycles -- so each unit can read from a sample until some specified condition is met (read depth, found a given mutation, etc). The units are also designed to talk to each other, enabling large jobs to truly be spread over multiple units (SeqHadoop? The OxNano Collective -- your sequences will be assimilated?).

Fundamentally, this is a very different vision of the future of sequencing than PGM. Very few biological instruments I've seen are designed to be packed en masse efficiently; Codon had stacks and stacks of off-the-shelf thermocyclers but their loading designs insisted on a racks that wasted lots of space. Such packing implies a large, centralized sequencing center. Each unit can take 96 samples, much as the PacBio can (and presumably OxNano will conveniently take 96-well plates, though in that form factor it isn't obvious how). Contrast this with the PGM, which requires each chip to be manually locked into the instrument. Perhaps PGM will later get a Big Brother, but for now it is clearly aimed at sequencing as a cottage industry.

Which gets back to an ongoing debate in science -- should science be done on a huge scale or by small teams. Should sequencers be present on every bench like a microcentrifuge or concentrated in big centers like a supercollider (or even like the autoclaves in an academic complex)? If sequencing is to become a routine and integral part of healthcare, will it be performed in doctors' offices or central labs? These will all be ongoing questions.

Of course, none of these reach the form factor we all dream of -- something the size & convenience of a tricorder.

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