— Cornell University researchers already have been
able to detect the mass of a single cell using submicroscopic
devices. Now they're zeroing in on viruses. And the
scale of their work is becoming so indescribably small
that they have moved beyond the prefixes "nano"
"pico" and "femto" to "atto."
And just in sight is "zepto."
of the Cornell research group headed by engineering
professor Harold Craighead report they have used tiny
oscillating cantilevers to detect masses as small
as 6 attograms by noting the change an added mass
produces in the frequency of vibration.
submicroscopic devices, whose size is measured in
nanometers (the width of three silicon atoms), are
called nanoelectromechanical systems, or NEMS. But
the masses they measure are now down to attograms.
The mass of a small virus, for example, is about 10
attograms. An attogram is one-thousandth of a femtogram,
which is one-thousandth of a picogram, which is one-thousandth
of a nanogram, which is a billionth of a gram.
work is an extension of earlier experiments that detected
masses in the femtogram range, including a single
E. coli bacterium, which recorded a mass of about
665 femtograms. For the latest experiments, the sensitivity
of the measurement was increased by reducing the size
of the NEMS cantilevers and enclosing them in a vacuum.
Eventually, the researchers say, the technology could
be used to detect and identify microorganisms and
latest experiment by Craighead and graduate research
assistant Rob Ilic is reported in the latest (April
1), issue of the Journal of Applied Physics.
The researchers manufactured the tiny cantilevers
out of silicon and silicon nitride. Imagine a diving
board 4 micrometers long and 500 nanometers wide.
Just as a diving board will vibrate if you jump on
it, these tiny cantilevers can be set into motion
by an applied electric field, or by hitting them with
a laser. The frequency of vibration can be measured
by shining a laser light on the device and observing
changing reflection of the light. The technology is
similar to that used last year in playing the newest
version of the Cornell nanoguitar, built to demonstrate
the potential of nanofabrication.
frequency of vibration of an object is, among other
things, a function of mass: A heavy guitar string
vibrates more slowly than a light one and produces
a lower tone. These tiny cantilevers vibrate at radio
frequencies, in the 1 to 15 megahertz range, and because
they are so small to begin with, adding just a tiny
bit more mass will make a measurable change in frequency.
cell detection, the researchers coated their cantilevers
with antibodies that bind to E. coli bacteria, then
bathed the devices in a solution containing the cells.
Some of the cells were bound to the surface, and the
additional mass changed the frequency of vibration.
In one case just one cell happened to bond to a cantilever,
and it was possible to detect the mass of the single
also have been used to bind virus particles or proteins
to a cantilever, the researchers say, but for the
experiment reported in the Journal of Applied Physics,
they attached tiny gold dots as small as 50 nanometers
in diameter to the ends of the cantilevers. The dots
then were exposed to a sulfur-based organic chemical
that naturally binds to gold, which formed a single
layer of a few hundred molecules on the surfaces of
the dots. From the frequency shift that resulted,
the researchers calculated that the mass added to
a typical 50-nanometer gold dot was 6.3 attograms.
testing various cantilever lengths and another type
of oscillator suspended between two points, they calculated
that the minimum resolvable mass would be .37 of an
attogram. They said that with refinements, the devices
could be extended to the zeptogram range, or one one-thousandth
of an attogram. The sensitivity is such that the devices
could be used to detect and identify DNA molecules,
proteins and other biological molecules by coating
the cantilevers with appropriate antibodies or other
materials that would bind to the targets. Ilic already
reports that "we have done viruses," although
that achievement is not reported in the current paper.
of the Journal of Applied Physics paper are Christopher
Ober, the F.N. Bard Professor of Metallurgical Engineering
at Cornell; Cornell graduate research assistant Wageesha
Senaratne; S. Krylovof Tel Aviv University; and P.
Neuzil of the Institute of Bioengineering and Nanotechnology
in Singapore. The experiments that detected masses
in the femtogram range were described in the Nov./Dec.
2001 issue of the Journal of Vacuum Science and Technology
by Ilic, Cornell graduate student David Czaplewski,
research associate Maxim Zalalutdinov, Craighead,
Neuzil, Cornell graduate student Christine Capagnolo
and Carl Batt, Liberty Hyde Bailey Professor of Food
Science at Cornell.
research was a project of Cornell's National Science
Foundation (NSF)-supported Nanobiotechnology Center,
using the equipment of the Cornell Nanoscale Facility,
also funded by the NSF.
Related World Wide Web sites: The
Craighead Research Group