High Speed Nanopore DNA Sequencing

DNA sequencing has come down in price in a spectacular fashion over the past decade. Yet, it’s still too expensive for everyday clinical use and mostly remains in the hands of scientists working in research labs. A promising approach that many have been trying to implement in order to speed up and reduce the cost of DNA sequencing is pushing the molecule through a tiny hole and using nearby electrodes to detect the unique change in the electric field as each nucleotide comes through.

This has been challenging for a variety of reasons, but researchers from Arizona State University and IBM’s T.J. Watson Research Center have overcome major obstacles that may help bring DNA sequencers to your local clinic. The major advancement was being able to use stationary electrodes, the gap between which doesn’t have to be constantly adjusted to identify the nucleotide coming through. Additionally, the relatively large nanopore they were able to use should allow the DNA molecules to more easily pass through, allowing for easier and faster reading of the sequence. So far the researchers have tested this technology on individual DNA bases and plan on being able to soon pass entire DNA molecules through the device.

Some details from an Arizona State University announcement:

“Previous attempts to make tunnel junctions for reading DNA had one electrode facing another across a small gap between the electrodes, and the gaps had to be adjusted by hand. This made it impossible to use computer chip manufacturing methods to make devices,” said [Stuart Lindsay, an ASU physics professor].

“Our approach of defining the gap using a thin layer of dielectric (insulating) material between the electrodes and exposing this gap by drilling a hole through the layers is much easier,” he said. “What is more, the recognition tunneling technology we have developed allows us to make a relatively large gap (of two nanometers) compared to the much smaller gaps required previously for tunnel current read-out (which were less than a single nanometer wide). The ability to use larger gaps for tunneling makes the manufacture of the device much easier and gives DNA molecules room to pass the electrodes.”

The team encountered considerable device-to-device variation, so calibration will be needed to make the technology more robust. And the final big step – of reducing the diameter of the hole through the device to that of a single DNA molecule – has yet to be taken.

But overall, the research team has developed a scalable manufacturing process to make a device that can work reliably for hours at a time, identifying each of the DNA chemical bases while flowing through the two-nanometer gap.

Study in ACS Nano: Fixed-Gap Tunnel Junction for Reading DNA Nucleotides…

Arizona State: ASU, IBM collaboration moves ultrafast, low-cost DNA sequencing technology one step closer to reality…