Scientists were able to trap a single particle between four microelectrodes, paving the way for a faster and cheaper way to sequence DNA. (Photo: Weihua Guan and Mark Reed) |
Sequencing
DNA base pairs — the individual molecules that make up DNA — is key for
medical researchers working toward personalized medicine. Being able to
isolate, study and sequence these DNA molecules would allow scientists
to tailor diagnostic testing, therapies and treatments based on each
patient’s individual genetic makeup.
But
being able to isolate individual molecules like DNA base pairs, which
are just two nanometers across — or about 1/50,000th the diameter of a
human hair — is incredibly expensive and difficult to control. In
addition, devising a way to trap DNA molecules in their natural aqueous
environment further complicates things. Scientists have spent the past
decade struggling to isolate and trap individual DNA molecules in an
aqueous solution by trying to thread it through a tiny hole the size of
DNA, called a “nanopore,” which is exceedingly difficult to make and
control.
Now
a team led by Yale University researchers has proven that isolating
individual charged particles, like DNA molecules, is indeed possible
using a method called “Paul trapping,” which uses oscillating electric
fields to confine the particles to a space only nanometers in size. (The
technique is named for Wolfgang Paul, who won the Nobel Prize for the
discovery.) Until now, scientists have only been able to use Paul traps
for particles in a vacuum, but the Yale team was able to confine a
charged test particle — in this case, a polystyrene bead — to an
accuracy of just 10 nanometers in aqueous solutions between quadruple
microelectrodes that supplied the electric field.
Their
device can be contained on a single chip and is simple and inexpensive
to manufacture. “The idea would be that doctors could take a tiny drop
of blood from patients and be able to run diagnostic tests on it right
there in their office, instead of sending it away to a lab where testing
can take days and is expensive,” said Weihua Guan, a Yale engineering
graduate student who led the project.
In
addition to diagnostics, this “lab-on-a-chip” would have a wide range
of applications, Guan said, such as being able to analyze how individual
cells respond to different stimulation. While there are several other
techniques for cell-manipulation available now, such as optical
tweezers, the Yale team’s approach actually works better as the size of
the targets gets smaller, contrary to other approaches.
The
team, whose findings appear in the May 23 Early Edition of the
Proceedings of the National Academy of Sciences, used charged
polystyrene beads rather than actual DNA molecules, along with a
two-dimensional trap to prove that the technique worked. Next, they will
work toward creating a 3-D trap using DNA molecules, which, at two
nanometers, are even smaller than the test beads. They hope to have a
working, 3-D trap using DNA molecules in the next year or two. The
project is funded by a National Institutes of Health program that aims
to sequence a patient’s entire genome for less than $1,000.
“This is the future of personalized medicine,” Guan said.
The
project was directed by Mark Reed (Yale University) and Predrag Krstic
(Oak Ridge National Laboratory). Other authors of the paper include Sony
Joseph and Jae Hyun Park (Oak Ridge National Laboratory).
Study abstract:
