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Two things make it difficult to measure
very tiny things: finding instruments that can sense changes on a
microscopic scale, and finding a way to convey these measurements to the
macro world.
A group of Princeton University researchers is
putting together arrays of microcantilevers that may eventually be capable
of measuring very small concentrations of molecules in environments like
blood vessels.
One key to the work is that the microcantilevers,
diving-board-like instruments that measure 10 microns wide and 100 to
1,000 microns long, are made of piezoelectric ceramic. This material gives
off current when it vibrates.
The amount of current is easy to
measure from the macro world, and the current correlates with the rate of
vibration. "The idea is when they oscillate up and down they introduce
charges on their surface which can be detected directly using
electronics," said Jeffrey Carbeck, assistant professor of chemical
engineering at Princeton.
The researchers have shown that the
microcantilevers can measure liquid viscosity and density. "As the fluid
[moves] faster there's going to be greater resistance for the cantilever
to bounce up and down, just like as you're driving down the road the
faster you go the more force there is on your hand [from the airstream] as
you tip it away from horizontal," said Carbeck.
The researchers
next step is using the cantilevers to sense whether specific molecules are
present in a liquid. They're working on applying a nanopore coating that
will increase the microcantilever surface area by 100 times. The coating
is a sort of 3-D honeycomb structure that has horizontal passages among
vertical honeycomb channels.
Molecules that bind specifically to
molecules of a substance to be measured can be embedded in these channels.
"It could be a DNA molecule that binds to another DNA molecule [or] it
could be a protein that recognizes some molecular signal of disease," said
Carbeck. As the embedded molecules pick up molecules of the substance, the
cantilever becomes heavier, which changes its rate of vibration.
There are two phases to the project, said Carbeck. "The first
phase, which I would qualify as the next three to five years, is making
these sensors fully functional, integrating the coating, integrating
receptors and actually allowing them to sense in a laboratory
environment."
As part of this, the researchers will also zero in
on the optimum size for the microcantilevers, which is somewhere between
one and 10 microns wide, said Carbeck. "One way to make it more and more
sensitive is to make it smaller," he said. This is because the heavier the
molecules are in relation to the microcantilever, the easier it is to
sense them, just as a diving board will oscillate more after a heavier
diver has jumped off.
But the cantilevers don't work if they're
too small. "As you start to make things very small... they start to lose
energy to the environment," said Carbeck. When this happens, "rather than
vibrating up and down at a well-defined frequency [it] becomes a range of
frequencies," he said. This means you can no longer correlate the motion
of the cantilever with the number of molecules captured on its surface, he
said.
Another technical challenge is depositing the coating.
"We're developing technologies for making very thin films out of this high
surface area coating. You have to get the coating less than one micron
thick... to be compatible with the one micron cantilever [and] also so it
does not crack when it dries," he said.
The researchers are
drawing together several existing technologies in new ways in order to to
form the sensors, said said Arun Majumdar, a mechanical engineering
professor at the University of California at Berkeley. "I think the idea
is good. The principal of using cantilevers is not new. Using
piezoelectric cantilevers to actuate is not new. But using piezoelectric
cantilevers to measure viscosity may be new [as well as] using
piezoelectric [cantilevers] with a honeycomb structure," said Majumdar.
Once the researchers put the pieces together, the microcantilevers
could be used to measure concentrations of molecules in laboratory
settings. They could also be used as an alternative to the cantilevers
used in atomic force microscopes, which are measured using laser beams,
said Carbeck. "You could... instead create surface force microscopy
cantilevers out of this material and detect the deflection electronically.
Also, [by] fabricating [cantilevers] into arrays you can sense a larger
area," he said.
The second phase is making these sensors
biocompatible, said Carbeck. "You want to figure out how to protect them
from things like the immune response of the body, which is to deposit
proteins and cells that form scar tissue on these materials. That's a
separate line of research... so you're talking about 10 years out before
you have a functional sensor that's also biocompatible," he said.
Ultimately, the project is aimed at developing arrays of
microcantilevers that can reside in the human body and measure several
different molecules or physical properties at once, said Carbeck. "You
would like to have sensors that can detect molecular signals of disease
that can be implanted in non-invasive way [in] say, the bronchiole of the
lungs or in microcapillaries or arteries,” he said.
The project
was initially funded by the National Science Foundation. The continuing
work to refine the microcantilevers and add the coating is funded by NASA.
Carbeck's colleagues in this work are Ilhan Aksay, Shilpa Bhansali, and
Jessica Jarvis.
A technical paper on the cantilevers' ability to
measure liquid viscosity and density has been accepted by the Journal of
Applied Physics. The researchers who worked on this paper were Wan Y.
Shih, of Drexel University and Princeton, Xiaoping Li, Huiming Gu and
Wei-Heng Shih of Drexel, and Aksay, who joined a second set of researchers
to publish a paper on the nanopore coating in the January 25, 2000 issue
of Langmuir. That group also included K. M. McGrath of the University of
Otago, D. M. Dabbs and N. Yao of Princeton, and K. J. Edler and S. M.
Gruner of Cornell University.
Timeline:
3-5 years, 10 years Funding: Government TRN
Categories: Applied Computing; MicroElectroMechanical Systems
(MEMS) Story Type: News Related Elements:
Photo 1, Photo 2, Technical paper, "Simultaneous Liquid Viscosity
and Density Determination with Piezoelectric Unimorph Cantilevers,"
accepted for publication, Journal of Applied Physics; Technical paper,"
Langmuir, January 25, 2000.
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