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New gene-extracting lab fits on a chip

no more secrets
By Charles Choi
New York (UPI) March 15, 2004
U.S. scientists said they have reduced all the elements of a genetics lab capable of extracting DNA from cells automatically onto a microprocessor the size of a dime.

Experts said the new invention could greatly advance the speed and efficiency of genetics work in academia, industry and government, in everything from medical analysis to scanning the genetic codes of whole ecosystems. The novel lab-on-a-chip already is finding use in probing stem cells, which contain the biological raw material of all other cells.

"We think it's going to be a tremendous labor saver," said biophysicist Stephen Quake of the California Institute of Technology in Pasadena, Calif.

"Automated systems already exist, but they take a fairly trained person to keep all the robots running," Quake told United Press International. "This chip is the first baby example of how we think biological automation is going to proceed, like going from vacuum tubes to microchips."

The chip requires thousands to millions times less of the expensive chemicals required to isolate and process nucleic acids such as DNA and RNA. Once commercialized, it could have a profound impact on the nucleic acid isolation market, which is worth $232 million per year in the United States alone. Current leaders in that market include Qiagen in Germany, Sigma-Aldrich in St. Louis and Amersham Biosciences in Britain.

"In a market where there is nothing else like this out there, it will be a system that researchers will be anxious to use," said analyst Sinead Igoe, of Frost & Sullivan, a research firm in New York City.

The lab-on-a-chip, which is called a microfluidic, is made cheaply from silicone rubber. It resembles a maze of plumbing, with thousands of pipes, chambers and valves scientists can program to open and close to mix contents.

"First you feed a cell into the input of the chip," Quake explained. "Then you close off the valves, enclose a small number of cells in the analysis chamber. You fill the other channels in the chip with various analytical agents. Then we open valves to the analysis chamber."

The cells are mixed with solutions that break down their components, after which the cell parts are flushed into a chamber that ensnares nucleic acids, to be held for later analysis. All steps in this procedure are automated.

Nucleic acid isolation normally requires from millionths to thousandths of a liter of expensive chemicals. The new chip only requires nanoliters -- or billionths of a liter. Quake suggested the device soon could make geneticists thousands of times more productive.

"We hope the impact will be enormous -- really change the way people do experiments," he said. "This is only the first, tiniest baby step along the way. There are substantial further challenges to be overcome, but we're optimistic."

Quake co-founded Fluidigm of San Francisco, which commercializes the microfluidic devices Quake and colleagues have invented. Among Fluidigm's investors are Lehman Brothers, General Electric, Eli Lilly and the government of Singapore. Its partners include GlaxoSmithKline. Igoe noted the U.S. microfluidics market was nearly $128 million in 2002 and is expected to grow to almost $710 million by 2008.

Quake said although Fluidigm has not yet commercialized the lab-on-a-chip, "I'm sure they'll use aspects of it very soon."

In the interim, Quake is making the chip available on a limited basis to close collaborators, and added that anyone could make the chip from plans described in the April issue of the journal Nature Biotechnology.

Among the Caltech scientists now using the microfluidic device are immunologist Ellen Rothenberg, who studies how blood cells form in the body, and bacteriologist Jared Leadbetter, who studies microbial diversity in the guts of termites.

The research team began work on the new chip when collaborator W. French Anderson, a stem cell investigator, came to Quake two years ago seeking to catalog stem cell genes. Stem cells are only available in limited numbers to researchers.

"This could help make the most of stem cells, where there are not a lot of samples out there," Igoe told UPI.

Also, because the device can extract genetic material from a single cell, it could allow researchers to examine all the germs scientists cannot grow in laboratories. An estimated 99 percent of microbe species cannot be cultivated for study.

"This could let us look at the genetics of all that 'biological dark matter' out there," Quake said.

He said he hopes future inventions could conduct more complex genetic analysis in the chip itself, such as measuring genetic expression in cells.

Igoe predicted the device someday could help forensics investigations as well.

"In the World Trade Center disaster, a large problem in identifying remains was most of the samples one would look at were destroyed. This could make the most of tiny samples," she said.

All rights reserved. Copyright 2004 by United Press International. Sections of the information displayed on this page (dispatches, photographs, logos) are protected by intellectual property rights owned by United Press International. As a consequence, you may not copy, reproduce, modify, transmit, publish, display or in any way commercially exploit any of the content of this section without the prior written consent of by United Press International.

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