Tiny piezoelectric cantilever sensors, similar to the one pictured here, are being calibrated by Drexel engineers to detect DNA.

A
tiny vibrating cantilever sensor could soon help doctors and field
clinicians quickly detect harmful toxins, bacteria and even indicators
of certain types of cancer from small samples of blood or urine.
Researchers from Drexel University are in the process of refining a
sensor technology that they developed to measure samples at the cellular
level into an accurate method for quickly detecting traces of DNA in
liquid samples.

According to lead researcher Dr. Raj Mutharasan,
a professor in Drexel’s College of Engineering, the group’s unique
application of lead zirconate titanate (PZT) to current
piezoelectric-excited cantilever sensor technology has created a way to
conduct more sensitive and timely tests for DNA. This DNA test will
allow for quick identification of harmful cells and bacteria.

“I
equate this new technology to authorities trying to catch a criminal
using latent fingerprints rather than a mug shot,” Mutharasan said. “It
is more precise, selective  and sensitive. With the PZT sensor we can
potentially detect DNA derived from a much smaller number of pathogens
and in a much shorter period of time than current methods.”

Cantilever sensor uses electric current for more sensitive measurements

Cantilever
sensor technology, which has been around for a little over a decade,
detects its minute targets using a method that is relatable to a
springboard bouncing with the movements of a diver.  The “board”—or
cantilever in this application—vibrates at a higher frequency when the
diver jumps off and his or her mass is removed. Conversely, the
vibration frequency of a cantilever would decrease when weight is added
to it. Measuring the difference in frequency of mass-free versus
mass-loaded vibrations allow researchers to detect cells or, in this
case, DNA, in samples.

Mutharasan
and his group combined the PZT material to the cantilever in an
innovative design, which allows researchers to initiate the
“springboard” effect by applying an electric current. This is an upgrade
over the classical cantilever method which requires an external
stimulus—a flick of the diving board—to set the system into motion.

Because
PZT sensors are completely controllable, Mutharasan’s group has
discovered high-order vibration modes in certain designs that are
sensitive to very small mass changes, on the order of one-billionth of a
microgram, in liquid samples.

“Such
high sensitivity enables us to measure biological molecules at a
million-fold more sensitive than what is currently feasible,” Mutharasan
said.

A second advantage: Rapid room-temperature replication of DNA

The
PZT cantilever device is dually useful because it speeds up the process
of replicating DNA in a sample. Replication is a necessary step in the
testing process in order to improve the quality of the sample and
positively identify the bacteria or cell of its origin, much like
growing bacterial culture. Muthrasan’s research group will conduct
simultaneous amplification and detection of DNA that is expected to be
carried out at room temperature and in a short time frame.

Typical
replication can be time-consuming because the sample needs to be heated
in order to begin the process. The advantage of the cantilever sensor
is that double-stranded DNA can be unwound by vibrating the sensor at
the proper frequency. This procedure essential step for replication can
cut a typical detection  process, which could take several hours, down
to less than an hour.

The
National Science Foundation recently awarded the team a grant to
continue research into simultaneous DNA replication and detection using
these piezoelectric vibrations. The key discovery that Mutharasan’s team
is building upon is its observation that DNA can be “melted”—a term
describing the process of unwinding a DNA strand for replication—by
application of mechanical energy to sensor surface via PZT.

With
the PZT sensor’s unique ability to test samples in liquids and at room
temperature, Mutharasan can foresee applications in detecting food and
water contamination, as well as use in the medical field. In early
testing the PZT sensor has successfully detected DNA indicators for
prostate cancer in urine samples, toxin-producing genes in pathogenic E. coli and an identifying gene of malaria-causing Plasmodium falciparum
in patient blood samples. The technology is still likely to be
three-to-five years from becoming commercially available for medical and
environmental uses, according to Mutharasan.

Source: Drexel University