Johns Hopkins researchers have devised a
self-assembling cube-shaped perforated container, no larger
than a dust speck, that could serve as a delivery system
for medications and cell therapy.
The relatively inexpensive microcontainers can be
mass-produced through a process that mixes electronic
chip-making techniques with basic chemistry. Because of the
cubic containers' metallic nature, their location in the
body could easily be tracked by magnetic resonance
imaging.
The method of making these self-assembling containers
and the results of successful lab tests involving the cubes
were reported in a paper published in the December issue of
the journal Biomedical Microdevices. In the tests,
the hollow cubes housed and then dispensed microbeads and
live cells commonly used in medical treatment.
"We're talking about an entirely new encapsulation and
delivery device that could lead to a new generation of
'smart pills,'" said
David H. Gracias, who led the lab team. "The
long-term goal is to be able to implant a collection of
these therapeutic containers directly at the site of an
injury or an illness."
Gracias is an assistant professor in the Whiting
School's Department of
Chemical and Biomolecular Engineering who focuses on
building micro- and nanosystems with medical applications.
He said he believes the microcontainers developed in his
lab could someday incorporate electronic components that
would allow the cubes to act as biosensors within the body
or to release medication on demand in response to a
remote-controlled radio frequency signal.
To make the self-assembling containers, Gracias and
his colleagues begin with some of the same techniques used
to make microelectronic circuits: thin film deposition,
photolithography and electrodeposition. These methods
produce a flat pattern of six squares, in a shape
resembling a cross. Each square, made of copper or nickel,
has small openings etched into it so that it eventually
will allow medicine or therapeutic cells to pass
through.
The researchers use metallic solder to form hinges
along the edges between adjoining squares. When the flat
shapes are heated briefly in a lab solution, the metallic
hinges melt. High surface tension in the liquified solder
pulls each pair of adjoining squares together like a
swinging door. When the process is completed, they form a
perforated cube. When the solution is cooled, the solder
hardens again, and the containers remain in their boxlike
shape.
"To make sure it folds itself exactly into a cube, we
have to engineer the hinges very precisely," Gracias said.
"The self-assembly technique allows us to make a large
number of these microcontainers at the same time and at a
relatively low cost."
The tiny cubes are coated with a very thin layer of
gold so that they are unlikely to pose toxicity problems
within the body. The microcontainers have not yet been
implanted in humans or animals, but the researchers have
conducted lab tests to demonstrate how they might work in
medical applications.
Gracias and his colleagues used micropipettes to
insert into the cubes a suspension containing microbeads
that are commonly used in cell therapy. The lab team showed
that these beads could be released from the cubes through
agitation. The researchers also inserted human cells,
similar to the type used in medical therapy, into the
cubes. A positive stain test showed that these cells
remained alive in the microcontainers and could easily be
released.
At the School of Medicine's
In Vivo Cellular and
Molecular Imaging Center, researcher Barjor Gimi and
colleagues then used MRI technology to locate and track the
metallic cubes as they moved through a sealed microscopic
S-shaped fluid channel. This demonstrated that physicians
will be able to use noninvasive technology to see where the
therapeutic containers go within the body. Some of the
cubes (those made mostly of nickel) are magnetic, and the
researchers believe it should be possible to guide them
directly to the site of an illness or injury.
The researchers are now refining the microdevices so
that they have nanoporous surfaces. Gimi, whose research
focuses on magnetic resonance microimaging of cell
function, envisions the use of nanoporous devices for cell
encapsulation in hormonal therapy. He also envisions
biosensors mounted on these devices for noninvasive signal
detection.
"We believe these self-assembling microcontainers have
great potential as a new tool for medical diagnostics and
treatment," Gracias said.
Lead author on the Biomedical Microdevices paper was
Gimi, a postdoctoral fellow in the
Russell H. Morgan Department of Radiology and Radiological
Science in the School of Medicine. Gracias served as
senior author. Co-authors were Timothy Leong, a doctoral
student in Chemical and Biomolecular Engineering; Zhiyong
Gu, a postdoctoral fellow in Chemical and Biomolecular
Engineering; Michael Yang, an undergraduate majoring in
biomedical engineering; Dmitri Artemov, an associate
professor in Radiology; and Zaver M. Bhujwalla, a professor
in Radiology and director of the In Vivo Cellular and
Molecular Imaging Center.
The research was supported in part by a grant from the
Johns Hopkins In Vivo Cellular and Molecular Imaging
Center, which is funded by the National Institutes of
Health.
The university has filed for a provisional patent
covering the self-assembling microcontainer technology.
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