NEW YORK, Sept 7 - The road to a better DNA chip is paved with gold, Northwestern University researchers report in the September 8 issue of Science .
Unlike current chip technologies, the gold nanoprobe does not require PCR amplification or fluorescence for DNA detection, so it will be simple, cheap, and sensitive enough to be used in a doctor’s office to diagnose disease, developer Chad Mirkin said.
“It’s the first technology that has a reasonable shot at displacing PCR for diagnostics,” Mirkin said. “Now you have a technology that has comparable sensitivity, superior selectivity and a lot less complexity when compared to fluorescents. And it’s cheaper.”
In the new method, Mirkin and his colleague Robert Letsinger, both of Northwestern University, treat target DNA-laden glass chips with tiny gold particles. And it is the gold nanoprobes that make these chips especially simple and inexpensive to read, Mirkin said.
Using the gold nanoprobe technology, Mirkin said chips can be developed like a photograph and read with an ordinary $60 flat-bed scanner available at Staples. Current PCR and fluorescence-based chips on the market require complex confocal microscopes that cost more than $60,000 to read them.
The silver in the photographic developing solution reacts with gold and amplifies the probe signal by as much as 100,000. As a result, the probes can detect as few as 60 double-stranded DNA molecules in a sample, which, according to Mirkin, may make expensive and time-consuming PCR amplification a thing of the past.
When the chips are run through the scanner, the perfect matches appear as gray dots. The darker the dot, the more target DNA there is.
To test the selectivity of the method, Mirkin used his chips to detect a single-base mismatch that some commercially available chips often miss.
The gold nanoprobe chip was able to discriminate between a perfect match and the “G:T wobble,” as the mismatch is known. The conventional fluorescence method was not able to detect the difference.
The chip, however, is unlikely to directly compete with chips like the Affymetrix GeneChip, which contains a high density of DNA probes.
Nanosphere, the company founded by Mirkin and Letsinger that holds the patent for the nanoprobe technology, plans to target the diagnostics market. This sector, Mirkin said, demands fewer probes per chip, making it easier to target. If Nanosphere were to decide to market high-density chip technology, they would likely have to partner with companies already in the sector since players such as Affymetrix hold many of the applicable patents.
So far, Nanosphere has raised “several million dollars” in venture capital and the company is currently trying to raise another $10 million in a second round of financing. Nanosphere plans to have alpha versions of the chip ready within a year.