In experiments that pave the way for tiny mobile
surgical tools activated by heat or chemicals,
Johns Hopkins researchers have invented dust particleŠsized
devices that can be used to grab and
remove living cells from hard-to-reach places without the
need for electrical wires, tubes or
batteries. Instead, the devices are actuated by thermal or
biochemical signals.
The mass-producible microgrippers measure
approximately one-tenth of a millimeter in
diameter each. In lab tests, they have been used to perform
a biopsylike procedure on animal tissue
placed at the end of a narrow tube. Experiments using the
devices were reported in the online early
edition of Proceedings of the National Academy of Sciences
for the week of Jan. 12.
Although the devices will require further refinement
before they can be used in humans, David
H. Gracias, who supervised the project, said that these
thermobiochemically responsive, functional
microtools represent a paradigm shift in engineering.
"We've demonstrated tiny inexpensive tools that
can be triggered en masse by nontoxic biochemicals," said
Gracias, an assistant professor of chemical
and biomolecular engineering in the Whiting School of
Engineering. "This is an important first step
toward creating a new set of biochemically responsive and
perhaps even autonomous micro- and
nanoscale surgical tools that could help doctors diagnose
illnesses and administer treatment in a more
efficient, less invasive way."
Today, doctors who wish to collect cells or manipulate
a bit of tissue inside a patient's body
often use microgrippers tethered to thin wires or tubes.
But these tethers can make it difficult to
navigate the tool through tortuous or hard-to-reach
locations. To eliminate this problem, the
untethered grippers devised by Gracias' team contain
gold-plated nickel, allowing them to be steered
by magnets outside the body. "With this method, we were
able to remotely move the microgrippers a
relatively long distance over tissue without getting
stuck," he said. "Additionally, the microgrippers
are triggered to close and extricate cells from tissue when
exposed to certain biochemicals or
biologically relevant temperatures."
The microgripper design — six three-jointed
digits extended from a central "palm" — resembles a
crab. (In fact, the joint design was inspired by arthropod
animals.) To fabricate the microgrippers in
their initial flat position with all digits fully extended,
the researchers employ photolithography, the
same process used to make computer chips. When the tiny
devices are inserted in the body and moved
magnetically, the gold-plated nickel in the palm and digits
will allow doctors to see and guide the
grippers with medical imaging units such as an MRI or
CT.
The microgrippers' grasping ability is rooted in the
chemical composition of the joints embedded
in the fingerlike digits. These joints contain thin layers
of chromium and copper with stress
characteristics that would normally cause the digits to
curl themselves closed like fingers clasping a
baseball. But the researchers added a polymer resin, giving
the joints rigidity to keep the fingers
from closing.
When the microgrippers arrive at their destination,
however, the researchers raise the
temperature to 104 degrees F, equivalent to a moderate
fever in humans. This heat softens the
polymer in the joints, causing the fingers to flex shut.
The researchers also found an alternative
method: Some nontoxic biological solutions can also weaken
the polymer and cause the grippers to
clamp down on their target.
In their lab experiments, the Johns Hopkins
researchers used a microgripper guided by a
magnet to grab and transport a dyed bead from among a group
of colorless beads in a water solution.
Team members also captured dozens of live animal cells from
a cell mass at the end of a capillary tube.
The cells were still alive 72 hours later, indicating that
the capture process did not injure them. Also,
the microgrippers captured samples from relatively tough
bovine bladder tissue.
The experiments showed that the tetherless
microgripper concept is viable and has great
potential for medical applications, the researchers said.
Gracias' team is now working to overcome
some remaining hurdles. As currently designed, each
biologically compatible gripper can close on a
target only once and cannot be reactivated to reopen and
release its contents. (A similar device from
the Gracias team, aimed at industrial microassembly
applications, can be directed to both capture and
release its load, but this requires chemicals that are not
safe for patients. This pick-and-place
microgripper was described in a recent article in the
Journal of the American Chemical Society.)
Gracias, who also is affiliated with the Institute for
NanoBioTechnology at Johns Hopkins, said
he hopes to collaborate with medical researchers who can
help move the microgrippers closer to use
as practical biopsy and drug-delivery tools in humans. In
September, he received a $1.5 million New
Innovators Award from the National Institutes of Health. He
plans to use the five-year grant to
develop an entire mobile, biochemically responsive micro-
and nanoscale surgical tool kit.
The lead author of the PNAS microgripper article was
Timothy G. Leong, who was a doctoral
student supervised by Gracias. In addition to Leong and
Gracias, the paper's co-authors, all students
supervised by Gracias, were Christina L. Randall, a
doctoral student in Biomedical Engineering; Brian R.
Benson, a junior supported by a Provost's Undergraduate
Research Award; Noy Bassik, who is enrolled
in an MD/PhD program involving the School of Medicine and
the Whiting School's Department of
Chemical and Biomolecular Engineering; and George M. Stern,
a master's degree student in Chemical
and Biomolecular Engineering.
The Johns Hopkins Technology Transfer staff has
obtained a provisional United States patent
covering the team's inventions and is seeking international
patent protection.
Funding for the research was provided by the National
Science Foundation, the National
Institutes of Health and the Dreyfus and Beckman
foundations.
To see a video of the microgrippers in action, go to:
www.jhu.edu/news/home09/jan09/gracias.html.
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