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Genome Researchers in the Chips
by Lindsey Arent
12:15 p.m. 28.Sep.99.PDT
Scientists have developed a method to create cheaper and more
efficient gene analysis chips using technology from an unlikely source
-- overhead projectors.
Researchers at the University of Wisconsin-Madison designed a chip
made of 480,000 tiny mirrors that can analyze thousands of genes at
once, and costs less than US$100.
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"With the chip, people will be able to study the genes much more
quickly and efficiently," said Roland Green, a postdoctoral fellow at
the university's biotechnology center and one of the project's lead
authors. "We want it to be accessible to any average sized lab."
Green and his team, which includes a professor of horticulture and
genetics, a physicist, and a semiconductor engineer, have created a
chip that does not require the specialized DNA-synthesis "masks"
that can take months to create and can cost several thousand dollars.
The team, whose research is published in the current issue of Nature
Biotechnology, created a technique called Maskless Array Synthesizer
that uses Digital Light Processor technology from Texas Instruments.
"We took the ability for digital slide projectors to pattern light, [and
used it] to pattern DNA chips," Green said. "Wherever you shine
light, that area becomes reactive. In an area the size of your fingernail
we'll have 500,000 DNA sequences.
Gene chip technology has traditionally used photolithography, a
process where ultraviolet light is projected through a series of
stenciled masks onto a glass chip. The result is the synthesis of
thousands upon thousands of specific DNA molecules, each of which
provides access to genetic information.
But with 100 custom masks often required to make a single chip that
addresses a specific aspect of genome analysis, the process can
become lengthy and costly, Green said.
Affymetrix, a Santa Clara, California firm, is one of the only makers
of such DNA chips, which cost between US$1,000 and $2,500.
Customized chips, containing DNA from a particular organism or
tissue, can range as high as $12,000 a pop.
The Affymetrix chips are designed to be non-reusable. Such high
costs often prevent smaller or more poorly funded labs from taking
advantage of cutting-edge DNA technology, Green said.
"If you want to make a new DNA chip, with a new sequence, you
have to build a new set of masks every time you want to make a new
design," he said. "That means it could cost $100,000 to make one."
When Green found that Affymetrix didn't make DNA chips for a plant
he was studying, he and his colleagues decided to make one of their
own. While brainstorming with a fellow professor about alternative
methods of analyzing DNA, the idea for using digital light
technology emerged.
Green and his team then applied Texas Instruments' overhead
projection technology to genetic analysis.
The technology revolves around 480,000 tiny aluminum mirrors
arranged on a computer chip. By manipulating the mirrors, Green and
his colleagues found that they could shine light in very deliberate
sequences, bypassing the need for the stenciled masks.
"We can set up a new chip design on your computer, instead of doing
it by hand," said Green. "It's much faster, we can make a custom chip
in one day, as opposed to months."
"The idea was so cheap and it worked so well that everybody told us
to commercialize the technology," he said.
Suddenly, a business was born. The Wisconsin team has applied for
a patent on the technology and founded a business to market the
technology, called NimbleGen Systems.
But some scientists are not as optimistic about the new technology,
citing numerous outdated attempts at making the perfect DNA chip.
"We're really early on in the hardware in developing these chips,"
said Dr. Edward Rubin, head of the Genome Sciences department at
Lawrence Berkeley National Laboratory. "There is an economic push
to generate something to accurately read large amounts of
information.
"What we use today will be thrown away tomorrow. There will be a
constant evolution in what people are using."
The chips will probably sell for about $50, Green said, providing
accessing to scientists regardless of their funding situation.
"We think this will be a tool that will allow small labs to get into
the DNA chip field." |
