New nanofluidics technology could revolutionize genetic analysis

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The new technology, called nanofluidics, was recently named one of the “most exciting” and influential Ten Emerging Technologies of 2009 by MIT’s Technology Review magazine.

Jointly developed by physics professor Robert Austin and engineering professor Stephen Chou, nanofluidics analyzes genetic material in several potentially useful ways using intricate metal chips with long, smooth, extremely narrow branching channels.

Austin explained that balls of stringy DNA isolated from single cells can then be threaded through the channels and are gently stretched out into one strand in the process.

“You slowly suck [the genetic material] into the tubes,” he said. “It’s like threading string through the eye of a needle. It’s difficult.”

With the molecule in this more readable form, Austin explained, scientists may get a chance to observe a single cell’s genes more easily.

According to Technology Review, this could mean that for “less than the cost of a chest x-ray,” physicians will soon be able to treat individual cancer cases better by looking at the genetic material of tumors. “The doctor could determine the particular genetic changes in the tumor cells and order the chemotherapy best suited to that variant,” the article explained.

This technology, which Chou said may usher in an era of personalized medicine, has been licensed since 2003 by the Philadelphia-based company BioNanomatrix, founded by Han Cao, a biologist in Chou’s lab.

Cao, the chief scientific officer of BioNanomatrix, said nanofluidics will eventually replace the dominant technique used to read information encoded in DNA, explaining that “inherently, it’s expensive and it’s inaccurate” to continue using today’s strategies.

Modern strategies for reading genes, he added, have produced a sequence of the human genome so incomplete and inaccurate that it has had to be revised 36 times since 2003. “But even in the 36th version [of the human genome], there are still many gaps and errors,” Cao said.

The promise of nanofluidics to keep genetic material intact while reading it is more useful now that “genetic analysis is not just about reading the bases” — the individual letters in the DNA’s instructions for building a person — anymore, he explained.

Instead, Cao said the new technology will emphasize major changes in the genome, including how many copies of a gene a person has or whether sections of the molecule have been accidentally inverted.

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“Its application will most likely be looking at large scale genomic rearrangement,” Cao explained.

“The use of [nanofluidics] will not be sequencing per se,” Austin explained. Unlike current ways of looking at DNA, the techniques they have developed will not be “ignoring the forest for the trees.”

The technology’s advantages stem from the fact that nanofluidics does not shred the genetic material into tens of thousands of pieces before reading it, said Edward Cox ’68, a molecular biology professor who contributed to the initial development of nanofluidics.

Since today’s sequencing techniques can only read small chunks of DNA, they must fragment the genetic material being analyzed. Those pieces then have to be joined together again, a process that is very error-prone.

Tearing genes apart in this process makes it difficult to determine how many copies of them an individual possesses or whether the genes have been erroneously duplicated — factors that influence people’s susceptibility to many diseases.

Because nanofluidics conserves genetic material more effectively, it will be particularly useful for figuring out which genes come from which parents, Cox added.

The development of nanofluidics took off 10 years ago, when Austin first teamed up with Chou, then a newcomer to Princeton.

“They have the expertise of measurement and DNA flow, [and] we have the expertise in making the channels,” Chou said, explaining that his colleague’s team had learned to observe and control the way DNA moved in fluid.

“Everyone came from different angles, but gradually we moved into the same target,” Chou said of the multidisciplinary development of nanofluidics. “We recognize that to apply [our knowledge] to biology, we have to understand the biology itself and the measurements [done by Austin].”

Though Cox said the technology has great potential, he added that he is uncertain it will capitalize on all of its promises because there are technical hurdles that still need to be overcome.

He does not think the new techniques will entirely supplant more established ones.

“[Sequencing technology] is here, and it’s working,” he said, referring to how current machines can already sequence some animal genomes in just a few hours.

One of the shortcomings of nanofluidics right now is that though it can prepare the genome to be read by straightening out the genetic material, the technology to actually sequence the DNA is not yet finished.

Many people, including Chou, have been trying to remedy that. “One thing that my lab is doing is to put nanoelectronic sensors in the channel,” he said. These very small sensors would be able to read the subtle changes in the electric field within the channel as different letters of the genetic code pass through.

But Cox said he is unsure how soon the readout system will be ready or if it will be finished at all. “There can be magic somewhere out there, but I don’t know where it is,” he said.