Credit: Univ. of Michigan |
With an invention that can be made from some of the same parts
used in CD players, Univ.
of Michigan researchers
have developed a way to measure the growth and drug susceptibility of
individual bacterial cells without the use of a microscope.
The new biosensor promises to speed treatment of bacterial
infections, said Raoul Kopelman, who is the Richard Smalley Distinguished Univ.
Professor of Chemistry, Physics and Applied Physics and a professor of
biomedical engineering, biophysics and chemical biology.
Instead of waiting days for culture results, clinicians will
be able to determine in minutes the antibiotic best able to treat the
infection. This advance, along with the sensor’s potential use in screening
existing and newly discovered compounds for antibiotic activity, could improve
patient outcome, reduce healthcare costs and reduce the spread of antibiotic
resistance
Because it also detects the response of individual cancer
cells, the sensor could someday be used as well in cancer drug development and
treatment. The research is reported in Biosensors
and Bioelectronics.
The device, called an asynchronous magnetic bead rotation
(AMBR) sensor, was invented in Kopelman’s lab at U-M. Early development of the
sensor, also in the Kopelman lab, was primarily the work of Brandon McNaughton,
who was a graduate student at the time. McNaughton went on to found the U-M
spinoff Life Magnetics Inc., where as chief technological officer he is further
developing the device.
The AMBR sensor uses a spherical, magnetic bead that
asynchronously spins in a magnetic field. Just as a pencil attached to a
child’s toy top creates drag that affects the way the top spins, anything
attached to the bead slows its rate of rotation. In the current work, the
researchers attached individual, rod-shaped Escherichia coli bacteria to
individual beads and watched what happened, using the newly developed AMBR
sensor.
“When one bacterium gets attached, it’s hanging out
there like a little hotdog, and it changes the drag tremendously, slowing down
the rate of rotation by a factor of four,” said Kopelman. “If the
bacterium grows even a tiny bit, the drag increases even more, and we can
monitor that nano-growth by observing changes in the rate of rotation.”
“The method can detect growth of as little as 80 nm,
making it far more sensitive than even a powerful optical microscope, which has
a resolution limit of about 250 nm,” said graduate student Paivo Kinnunen,
one of the paper’s lead authors, who is also working at Life Magnetics while
completing his studies. (While the AMBR sensor does not require a microscope,
one was used in the current study to confirm results).
The U-M group demonstrated that the sensor not only can
monitor the growth of a single bacterium throughout its life cycle and over
multiple generations, but it can also determine when an individual bacterium
stops growing, in response to treatment with an antibacterial drug, for
instance.
“You can basically tell, within minutes, whether or not
the antibiotic is working,” said Kinnunen.
In the near future, “we expect it will be possible to
make the determination even quicker,” said graduate student Irene Sinn,
the paper’s other lead author. “This is something we are actively working
on.”
The device also can be used for monitoring the growth and
drug susceptibility of other types of cells, said Kinnunen. “The sensor is
very sensitive to small changes in growth, so this method can be applied to any
applications in the microscale or nanoscale where there are small changes in
size. That includes the growth of yeast and cancer cells as well as
bacteria.”
The technology could have far-reaching implications, said
McNaughton.
“At Life Magnetics we are very excited and optimistic
about leveraging the single cell sensitivity of the AMBR technology to develop
a product that will determine the best antimicrobial in hours instead of
days,” he said. “This will have a dramatic positive impact for
patients and for the health system, cutting costs and saving lives.
Inappropriate therapy and the overuse of antimicrobials are large contributors
to the problem of increased resistance in bacteria. In fact, with superbugs
such as MRSA causing every year in the U.S. more deaths than HIV/AIDS, it
is no surprise that the Centers for Disease Control and Prevention considers
antimicrobial resistance to be among the most pressing health problems. Our
technology is designed to attack that problem.”
In addition to Kopelman, Kinnunen, Sinn and McNaughton, the
paper’s authors are Duane Newton, associate professor of pathology and director
of the microbiology/virology laboratory, and Mark Burns, professor and chair of
chemical engineering.
