Using Strain to Read DNA

Geneticists may soon use a new type of strain sensor to sequence DNA faster and cheaper than anything they now have in their labs.

by Alan Brown
June 26, 2017

A new type of strain sensor could sequence faster and at lower cost that existing technologies. The approach could make it more economical to sequence individual genomes in order to find the best match of medicines, or to solve crimes using forensic genetic evidence.

It also shows how researchers could use new materials, molecular engineering, and simulation to create entirely new types of technologies.

DNA has a ladder-like structure. The rungs on the ladder consist of only four bases. Each base binds with only one other base: cytosine with guanine, thymine with adenine.

Conventional DNA sequencing involves breaking the ladder rungs to form an individual strand, then copying, labeling and reassembling pieces of DNA to read the genetic information.

For 20 years, researchers have tried pulling DNA through porous materials and reading the electrical charges on the bases as they pass. This produces an electrical signal, but it has been too weak to read accurately.

Finding the signal

A new proposal, based on a simulation created by the National Institute of Standards and Technology and University of Groningen, puts an interesting twist on this.

It starts by drilling pores in graphene, an atomically thin sheet of carbon that converts mechanical strain to current. It attaches several of the same base, such as cytosine, to the pore. The sensor then goes into a solution of single DNA strands. Turning on a current creates a potential that pulls the strands through the pores.

Whenever a guanine base passes through a pore, its hydrogen atom bonds with a cytosine. As the DNA strand continues to move past the pore, the bond yanks the graphene and then snaps. This creates a mechanical strain in the graphene that turns into an electrical current.

This signal, according to the group’s simulation, will fall into the milliampere range. This is far greater than past nanopore experiments, and large enough to read accurately.

By stacking four graphene sensors, one for each base, on top of each, the team could read an entire DNA molecule. They believe that any one sensor would be 90 percent accurate and produce no false positives. Further, the four independent readings of a single strand could achieve 99.99 percent accuracy.

Everything takes place in water at room temperature. The system has the potential to measure roughly 66 million DNA bases per second, without advanced data processing, microscopes, or restrictive operating conditions. Other than attaching bases to the nanopore, other research groups have demonstrated all sensor components experimentally. The system could also work with other strain-sensitive materials, such as molybdenum disulfide.