Discovery could help bring down price of DNA sequencing

In May, Nobel Laureate James D. Watson, the scientist who co-discovered the structure of DNA, became the first person to receive his own complete personal genome -- all three billion base pairs of his DNA code sequenced. The cost was $1 million, and the process took two months.

A million dollars for a map of all your genes is way out of reach for most people. The National Institutes of Health would like to bring it down to $1,000 by the year 2014, but plenty of technological hurdles remain before you’ll be able to secure your genetic blueprint for this more affordable price.

One promising method for speeding up DNA sequencing, and thus reducing its cost, is nanopore sequencing, where DNA moves through a tiny hole, much like thread going through a needle. The technique can detect individual DNA molecules, but the DNA gallops through so fast that it is impossible to read the individual letters, or bases, and determine the sequence. (The four letters of the genomic alphabet are A, T, G and C, each representing one of the base nucleotides that make up DNA.)

Using a theory based on classical hydrodynamics, a Northwestern University researcher now has explained the nature of the resistive force that determines the speed of the DNA as it moves through the nanopore, which is just five to 10 nanometers wide. (One nanometer is a billionth of a meter.) This understanding could help scientists figure out how to slow the DNA down enough to make it readable and usable -- for medical and biotechnology applications, in particular.

Sandip Ghosal, associate professor of mechanical engineering in Northwestern’s McCormick School of Engineering and Applied Science, is the first to apply classical hydrodynamics to the interaction of DNA with a nanopore. The findings, an important step toward achieving single-base resolution in nanopore sequencing, were published in the June 8 issue of the journal Physical Review Letters (PRL).

“DNA is pulled through the nanopore’s channel by an electric force, but there also is a resistive force,” said Ghosal, sole author of the PRL paper. “My idea was that the resistance was coming from fluid friction, which could explain the speed measurements taken in experimental studies.”

In Ghosal’s explanation, the DNA pulls some of the fluid surrounding the molecule through the channel with it. The lubrication forces arising in this fluid layer create the resistance that opposes the electrical pulling force. Ghosal’s calculations in the PRL paper show that his theoretical model is consistent with experimental results and explains the DNA’s speed.

“Understanding the mechanics of DNA translocation will allow scientists to make alterations, to figure out how to apply more friction,” said Ghosal, who has proposed using a coating on the channel walls to slow down the flow of the DNA. Source : Northwestern University