In a Nature Nanotechnology cover article, researchers from Harvard and the Massachusetts Institute of Technology demonstrated that a long DNA molecule can be pulled through a graphene nanopore. |
Scientists
are one step closer to a revolution in DNA sequencing, following the
development in a Harvard lab of a tiny device designed to read the
minute electrical changes produced when DNA strands are passed through
tiny holes—called nanopores—in an electrically charged membrane.
As
described in Nature Nanotechnology, a research team led by Charles
Lieber, the Mark Hyman Jr. Professor of Chemistry, have succeeded for
the first time in creating an integrated nanopore detector, a
development that opens the door to the creation of devices that could
use arrays of millions of the microscopic holes to sequence DNA quickly
and cheaply.
First
described more than 15 years ago, nanopore sequencing measures subtle
electrical current changes produced as the four base molecules that make
up DNA pass through the pore. By reading those changes, researchers can
effectively sequence DNA.
But
reading those subtle changes in current is far from easy. A series of
challenges—from how to record the tiny changes in current to how to
scale up the sequencing process—meant the process has never been
possible on a large scale. Lieber and his team, however, believe they
have found a unified solution to most of those problems.
“Until
we developed our detector, there was no way to locally measure the
changes in current,” Lieber said. “Our method is ideal because it is
extremely localized. We can use all the existing work that has been done
on nanopores, but with a local detector we’re one step closer to
completely revolutionizing sequencing.”
The
detector developed by Lieber and his team grew out of earlier work on
nanowires. Using the ultra-thin wires as a nanoscale transistor, they
are able to measure the changes in current more locally and accurately
than ever before.
“The
nanowire transistor measures the electrical potential change at the
pore and effectively amplifies the signal,” Lieber said. “In addition to
a larger signal, that allows us to read things much more quickly.
That’s important because DNA is so large [that] the throughput for any
sequencing method needs to be high. In principle, this detector can work
at gigahertz frequencies.”
The
highly localized measurement also opens the door to parallel
sequencing, which uses arrays of millions of pores to speed the
sequencing process dramatically.
In
addition to the potential for greatly improving the speed of
sequencing, the new detector holds the promise of dramatically reducing
the cost of DNA sequencing, said Ping Xie, an associate of the
Department of Chemistry and Chemical Biology and co-author of the paper
describing the research.
Current
sequencing methods often start with a process called the polymerase
chain reaction, or DNA amplification, which copies a small amount of DNA
thousands of millions of times, making it easier to sequence. Though
critically important to biology, the process is expensive, requiring
chemical supplies and expensive laboratory equipment.
In
the future, Xie said, it will be possible to build the nanopore
sequencing technology onto a silicon chip, allowing doctors,
researchers, or even the average person to use DNA sequencing as a
diagnostic tool.
The
breakthrough by Lieber’s team could soon make the transition from lab
to commercial product. The Harvard Office of Technology Development is
working on a strategy to commercialize the technology appropriately,
including licensing it to a company that plans to incorporate it into
their DNA sequencing platform.
“Right
now, we are limited in our ability to perform DNA sequencing,” Xie
said. “Current sequencing technology is where computers were in the ’50s
and ’60s. It requires a lot of equipment and is very expensive. But
just 50 years later, computers are everywhere, even in greeting cards.
Our detector opens the door to doing a blood draw and immediately
knowing what a patient is infected with, and very quickly making
treatment decisions.”
Local electrical potential detection of DNA by nanowire–nanopore sensors
