Saturday, February 27, 2010

Low-Cost DNA Sequencing Tool with Carbon Nanotubes for Medical Diagnostics

This visualization depicts the flow of ions and DNA through a single-walled carbon nanotube. Instruments based on the concept could one day be a common fixture in doctors' offices. 

Photo courtesy of Hao Liu, Arizona State University.

Researchers working toward a low-cost DNA sequencing tool for medical diagnostics and other uses have proposed a microfluidic device that uses a single-walled carbon nanotube as a nanopore conduit to thread, or translocate, a single strand of DNA from one reservoir with electrolyte to another, analyzing and sequencing the DNA in the process.

The Arizona State and Columbia University team turned to the Physics Division's Predrag Krstic to explain unexpected results when they measured the translocation current of material through the nanotube.

In such a device, the negatively charged DNA material, which is immersed in an electrolytic fluid, is propelled, so to speak, through the nanotube by an electric field. When the Arizona State team measured the current flowing through the nanotube, they were baffled by the data.

"They were surprised by the current of electrolytic ions that was orders of magnitude higher than any prediction," Predrag says. "That's where we came into the project."

Predrag and former ORNL researcher Sony Joseph performed atomistic molecular and fluid dynamics simulations at the University of Tennessee's National Institute for Computational Sciences, located at ORNL.

A National Institutes of Health initiative toward a "$1,000 sequencer" is driving the development of these types of microfluidic technologies, which would allow doctors to quickly analyze segments of DNA for traits that could be precursors, or causes, of disease. Such a doctor's office instrument would be an invaluable tool for diagnosing and treating genetically based conditions.

Krstic and Joseph, in a paper published with their ASU and Columbia collaborators in the Jan. 1, 2010, issue of Science, attributed the mysterious current surge to the "slipping" of water molecules through the perfect and hydrophobic inner surface of the carbon nanotube and to trapped electrical charge.

Understanding such phenomena is key to the development of these single-molecule-detection instruments that would be inexpensive enough to become common in doctor's offices.
Predrag notes that almost a decade ago, a similar approach to threading single strands of DNA for high-throughput sensing established groundwork for the nanopore approach. 

ORNL's Thomas Thundat and James Lee pioneered and patented nanogap fabrication by electrolytic deposition of metal nanoelectrodes, which would enable sequencing based on reading of transverse electron tunneling current when a DNA strand is shepherded through the nanogap.

The ASU-Columbia approach relies on the single-walled carbon nanotube as the conduit. The concept has received Recovery Act funding through the NIH's "Grand Opportunities" initiative (the goal of a $1,000 sequencer) for the ASU, Columbia and ORNL effort.

"This is an example of how the front of science is increasingly multidisciplinary, with contributions by experimentalists and theorists in atomic and solid-state physics, chemistry, biology and engineering," says Predrag.

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