Fwd: [GRG] Microfluidics Technique to Sequence Genomes for $100 in Five Years

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Bryan Bishop

Feb 28, 2009, 12:41:38 PM2/28/09
to diy...@googlegroups.com, kan...@gmail.com
Microfluidics paper archive:

In other words, this same type of microfluidic device can be printed
by an inkjet printer, or laminated, or done with another technique
that I am testing in the lab today :-). There are also some papers on
alternatives to gel electrophoresis using microfluidics. Anyway, have

- Bryan
1 512 203 0507

---------- Forwarded message ----------
From: L. Stephen Coles, M.D., Ph.D. <sco...@grg.org>
Date: Sat, Feb 28, 2009 at 10:36 AM
Subject: [GRG] Microfluidics Technique to Sequence Genomes for $100 in
Five Years
To: Gerontology Research Group <g...@lists.ucla.edu>

To Members and Friends of the Los Angeles Gerontology Research Group:

        This just in from Cliff H.  Microfluidics methods to sequence
genomes for $100 in five years... -- Steve Coles

"TR10: $100 Genome:

Han Cao's Nanofluidic
Chip Could Cut DNA Sequencing Costs Dramatically"
Lauren Gravitz, MIT Technology Review (March/April 2009)

Nanoscale sorting: A tiny nanofluidic chip is the key to
BioNanomatrix’s effort to sequence a human genome for just $100.
Credit: Bionanomatrix
  BioNanomatrix cofounder Han Cao discusses why nanofluidic chips
could revolutionize genome sequencing.

February 28, 2009;  In the corner of the small lab is a locked door
with a colorful sign taped to the front: "$100 Genome Room--Authorized
Persons Only." BioNanomatrix, the startup that runs the lab, is
pursuing what many believe to be the key to personalized medicine:
sequencing technology so fast and cheap that an entire human genome
can be read in eight hours for $100 or less. With the aid of such a
powerful tool, medical treatment could be tailored to a patient's
distinct genetic profile.

        Despite many experts' doubt that whole-genome sequencing could
be done for $1,000, let alone a 10th that much, BioNanomatrix believes
it can reach the $100 target in five years. The reason for its
optimism: company founder Han Cao has created a chip that uses
nanofluidics and a series of branching, ever-narrowing channels to
allow researchers, for the first time, to isolate and image very long
strands of individual DNA molecules.  If the company succeeds, a
physician could biopsy a cancer patient's tumor, sequence all its DNA,
and use that information to determine a prognosis and prescribe
treatment -- all for less than the cost of a chest x-ray. If the
ailment is lung cancer, for instance, the doctor could determine the
particular genetic changes in the tumor cells and order the
chemo­therapy best suited to that variant.

        Cao's chip, which neatly aligns DNA, is essential to cheaper
sequencing because double-stranded DNA, when left to its own devices,
winds itself up into tight balls that are impossible to analyze. To
sequence even the smallest chromosomes, researchers have had to chop
the DNA up into millions of smaller pieces, anywhere from 100 to 1,000
base pairs long. These shorter strands can be sequenced easily, but
the data must be pieced back together like a jigsaw puzzle. The
approach is expensive and time consuming. What's more, it becomes
problematic when the puzzle is as large as the human genome, which
consists of about three billion pairs of nucleo­tides. Even with the
most elegant algorithms, some pieces get counted multiple times, while
others are omitted completely. The resulting sequence may not include
the data most relevant to a particular disease.

        In contrast, Cao's chip untangles stretches of delicate
double-stranded DNA molecules up to 1,000,000 base pairs long -- a
feat that researchers had previously thought impossible. The series of
branching channels gently prompts the molecules to relax a bit more at
each fork, while also acting as a floodgate to help distribute them
evenly. A mild electrical charge drives them through the chip,
ultimately coaxing them into spaces that are less than 100 nanometers
wide. With tens of thousands of channels side by side, the chip allows
an entire human genome to flow through in about 10 minutes. The data
must still be pieced together, but the puzzle is much smaller (imagine
a jigsaw puzzle of roughly 100 pieces versus 10,000), leaving far less
room for error.

Sequencing DNA: Thousands of branching channels just nanometers wide
(left) untangle very long DNA strands;
bright fluorescent labels allow researchers to easily visualize these
molecules (right).  Credit: Bionanomatrix

        The chip meets only half the $100-genome challenge: it
unravels DNA but does not sequence it. To achieve that, the company is
working with Silicon Valley-based Complete Genomics, which has
developed bright, fluorescently labeled probes that bind to the 4,096
possible combinations of six-letter DNA "words." Along with
­BioNanomatrix's chip, the probes could achieve the lightning-fast
sequencing necessary for the $100 genome. But the probes can't stick
to double-stranded DNA, so Complete Genomics will need to figure out
how to open up small sections of DNA without uncoupling the entire

         BioNanomatrix is keeping its options open. "At this point, we
don't have any exclusive ties to any sequencing chemistry," says Gary
Zweiger, the company's vice president of development. "We want to make
our chip available to sequencers, and we feel that it is an essential
component to driving the costs down to the $100 level. We can't do it
alone, but we feel that they can't do it without this critical

        Whether or not BioNanomatrix reaches its goal of $100
sequencing in eight hours, its technology could play an important role
in medicine. Because the chips can process long pieces of DNA, the
molecules retain information about gene location; they can thus be
used to quickly identify new viruses or bacteria causing an outbreak,
or to map new genes linked to specific diseases. And as researchers
learn more about the genetic variations implicated in different
diseases, it might be possible to biopsy tissue and sequence only
those genes with variants known to cause disease, says Colin Collins,
a Professor at the Prostate Center at Vancouver General Hospital, who
plans to use BioNanomatrix chips in his lab. "Suddenly," Collins says,
"you can sequence extremely rapidly and very, very inexpensively, and
provide the patient with diagnosis and prognosis and, hopefully, a

Ref.: http://www.technologyreview.com/biomedicine/22112/

L. Stephen Coles, M.D., Ph.D., Co-Founder
Los Angeles Gerontology Research Group
URL: http://www.grg.org
E-mail: sco...@grg.org
E-mail: sco...@ucla.edu

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Jeswin John

Feb 28, 2009, 12:48:13 PM2/28/09
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what's on the .zip file? At 20 kbps, it will take me 40 minutes.
Join the Revolution

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