A scanning electron microscope image shows a bundle of ‘microworms’ produced using a vapor-deposition process developed by researchers at MIT and Northeastern. Photo courtesy of Gleason Lab |
Researchers at MIT and Northeastern have
come up with a new system for monitoring biomedical indicators—such as levels
of sodium or glucose in the blood—that could someday lead to implantable
devices that would allow, for example, people with diabetes to check their
blood sugar just by glancing at an area of skin.
A number of researchers have developed
microparticle-based systems for monitoring biomedical conditions or for the
selective delivery of drugs to certain organs or areas of the body. But one
drawback of these systems is that the particles are small enough to be swept
away from the initial site over time. The new system involves a different kind
of microparticle that can avoid this problem.
While traditional particles are
spherical, the new particles are shaped like long tubes. The tubes’ narrow
width, which is comparable to that of the previously studied microparticles,
keeps the tubes’ contents in close proximity to blood or body tissue, making it
easy for the particles to sense and respond to chemical or other conditions in
their surroundings. The tubes’ relatively greater length keeps the tubes very
well anchored in place for long-term monitoring, perhaps for months on end.
The particles eventually could be used
to monitor the glucose levels of diabetics or the salt levels of those with a
condition that can cause swings in blood salt concentrations.
The new findings are being reported in
the journal Proceedings of the National
Academy of Sciences. It was co-authored by Karen Gleason, the
Alexander and I. Michael Kasser Professor of Chemical Engineering at MIT;
Heather Clark, professor of pharmaceutical science at Northeastern University;
MIT postdoctoral researcher Gozde Ozaydin-Ince; and Northeastern doctoral
student J. Matthew Dubach.
The process of creating the new
nanoparticles is an offshoot of Gleason’s work on a method of coating materials
by vaporizing the coating material and letting it deposit on a surface to be
coated. In work published last month, she and her co-workers had shown that
this technique—called chemical vapor deposition (CVD)—could be used to coat a
material containing microscopic pores, thus making the pores even smaller and
giving them a surface that could respond to the chemical properties of materials
passing through them.
This new work uses CVD to coat an
aluminum oxide layer that has been etched to contain tiny pores, and, as in the
previous work, the coating extends down onto the walls of these pores. But then
the coated material itself is dissolved away, leaving just a series of hollow
tubes where the pores used to be. Before that, though, another material can be
added—something that responds to the environment, or a drug to be delivered,
for example. The tubes are then capped at either end.
Gleason explains that these
“microworms,” as she calls them, can then be injected under the skin to form a
fluorescent “tattoo.” By filling the tiny hollow tubes with a material that
fluoresces in response to the presence of a specific chemical, “the degree of
fluorescence provides continuous physiological monitoring of a specific
chemical” in the body, and can be monitored right through the skin. The light
emitted by the fluorescing chemical “is visible to the human eye, and thus can
be directly interpreted by the patient without the need for bulky monitors,”
she says.
While the initial microworms were made
to detect salt levels, and were successfully tested in mice, there are a
variety of potential applications, Gleason says. One significant possibility is
measuring glucose levels: “Tight control over glucose levels can help
individuals stave off the devastating side-effects of diabetes, the number one
cause of kidney failure, blindness in adults, nervous system damage, and
amputations and also a major risk factor for heart failure, stroke and birth
defects,” she says. Diabetes currently affects more than 20 million people in
the U.S.,
and that is expected to double in 25 years.
The tubes are so tiny—about 200 nm
across—that “the body doesn’t even think they’re there,” Gleason says, allowing
them to operate in “stealth mode” without triggering any physical response.
Raoul Kopelman, the Richard Smalley
Distinguished University Professor of Chemistry, Physics and Applied Physics
and Research Professor of Biomedical Engineering at the Univ. of Michigan,
calls this “high quality work by an expert team,” and says, “In principle, this
could open the way for avoiding blood tests, which need a central lab, expert
nurses, extra time and extra costs. It could be done in a doctor’s office, or
even at home. It will also avoid complications for patients with ‘difficult,’
or ‘used-up’ veins, patients on blood thinners, etc.” However, he cautioned
that “The biggest stumbling block is the safety factor, i.e. FDA approval. FDA
might not only worry about long-term chemical toxicity and bio-elimination, but
also about complications—i.e., could it trigger blood clots?”
In addition to the fact that these
microworms stay in place when injected into the body, their manufacturing
process itself provides a significant advantage, Gleason says. Because CVD is a
standard manufacturing method used in the semiconductor industry, the
manufacture of these devices should be relatively easy and inexpensive.
Gleason says, “One can imagine using
these kinds of tubes to shrink-wrap just about anything,” including drugs that
could be delivered slowly over time through small openings in the tubes.
