This is the NIST concept for DNA sequencing through a graphene nanopore. Credit: Smolyanitsky/NIST
Researchers at NIST have simulated a new concept for rapid, accurate gene sequencing by pulling a DNA molecule through a tiny, chemically activated hole in graphene and detecting changes in electrical current. The method could identify about 66 billion bases/s with 90% accuracy and no false +ves. If demonstrated experimentally, the NIST method might ultimately be faster and cheaper than conventional DNA sequencing, meeting a critical need for applications such as forensics.
Conventional sequencing, developed in the 1970s, involves separating, copying, labeling and reassembling pieces of DNA to read the genetic information. The new proposal is a twist on the more recent “nanopore sequencing” idea of pulling DNA through a hole in specific materials, originally a protein. This concept- pioneered 20 years ago at NIST- is based on the passage of ions through the pore. The idea remains popular but poses challenges such as unwanted electrical noise, or interference, and inadequate selectivity.
By contrast, NIST’s new proposal is to create temporary chemical bonds and rely on graphene’s capability to convert the mechanical strains from breaking those bonds into measurable blips in electrical current. “This is essentially a tiny strain sensor,” says NIST theorist Alex Smolyanitsky.
A graphene nanoribbon (4.5 x 15.5 nm) has several copies of a base attached to the nanopore (2.5 nm wide). In simulations of how the sensor would perform at room temperature in water, cytosine is attached to the nanopore to detect guanine. A single-strand (unzipped) DNA molecule is pulled through the pore. When guanine passes by, hydrogen bonds form with the cytosine. As the DNA continues moving, the graphene is yanked and then slips back into position as the bonds break. The temporary changes in electrical current indeed indicate that a target base has just passed by. To detect all 4 bases, 4 graphene ribbons, each with a different base inserted in the pore, could be stacked vertically to create an integrated DNA sensor.
Signal strength was in the milliampere range, stronger than in the earlier ion-current nanopore methods. Based on the performance of 90% accuracy without any false positives, the 4 independent measurements of the same DNA strand would produce 99.99% accuracy, as required for sequencing the human genome. http://www.nist.gov/mml/acmd/nist-simulates-fast-accurate-dna-sequencing-through-graphene-nanopore.cfm
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