A nifty paper in yesterday's online edition of PNAS could presage the future of microfluidics development -- not to mention of sequencing technology. Richard Mathies of the University of California, Berkeley, and colleagues report the development of an integrated chip capable of performing the complete Sanger sequencing protocol, from template to gel.

Lab-on-a-chip, or microfluidic devices, have been long been heralded as the future of life science research. We profiled the technology last year in our feature on "Seven technologies that are transforming the life sciences."

Most existing microfluidic chips have been fairly rudimentary affairs, however, tackling such "low-hanging fruit" as simple electrophoretic separations and sample cleanup, for instance. It's actually been possible to run sequencing separations themselves on microfluidic platforms for at least a decade. But that was using reactions that were performed off-line. With this latest development, that step has now been integrated onto the chip.

From 1 femtogram of starting material in a 250-nanoliter reaction, the system (built of glass and rubbery polydimethylsiloxane) performs thermal cycling, sample purification, and capillary electrophoresis to produce some 556 continuous bases of sequence at 99% accuracy.

That's a bit on the short side for traditional Sanger sequencing, where reads can top 800 bases per run, but is far longer than that given by new technologies from 454 Life Sciences, for instance. The authors indicate they are working to reduce template requirements 10-fold, to 100 attomoles, and say they could possibly go even lower. At those levels, they continue, it should be possible to sequence PCR fragments directly, rather than having to clone them first -- a development that would remove one of the chief shortcomings of Sanger sequencing relative to these newer methods.

Indeed, the authors say they "are working toward a Microbead Integrated DNA Sequencer (MINDS) that parses PCR-colony beads into discrete thermal cycling chambers coupled to purification and electrophoretic separation to produce a fully integrated genome-center-on-a-chip."

Mathies is a consultant with Microchip Biotechnologies Inc., a company that is working to commercialize microchip sequencing technologies and may therefore benefit from the results of this research.