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IBM and university researchers uncover a new biomechanical
phenomenon using tiny silicon fingers
"Micromachines" could lead to new medical treatments, nano-robots
Zurich/Basel, Switzerland, April 13, 2000 — Scientists
from IBM Research and the
University of Basel have found a new approach for using tiny
biochemical "machines" made of silicon to detect defects
in DNA, which could eventually lead to new medical treatments.
As reported in the April 14 issue of the journal Science,
the researchers discovered that DNA bends tiny silicon "fingers"
that have a thickness of less than a 1/50 of a human hair. Using
a process called "molecular recognition," in which molecules
bind according to a key-lock mechanism, an array of fingers or cantilevers
arranged like the teeth of a comb was made attractive to specific
DNA codes and proteins. By observing the way different cantilevers
bend as the DNA adhered to them, the researchers were able to detect
the tiniest possible defect in a DNA sequence, a so-called single
base mismatch. Advantages of the new technology are direct detection
of the targeted substance, and it has good sensitivity even for
small molecules.
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Array of tiny cantilevers
imaged by scanning electron microscopy. |
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The cantilevers bend by docking
of molecules. |
"This biomechanical technique has the potential to enable
fast and cheap biochemical analysis, and could be used for mobile
applications," said Christoph Gerber of IBM Research. "For
example, there is a need for rapid diagnosis of the condition that
is a leading cause of sudden death—heart attack. If the technology
can be developed as we hope, it could make it possible to determine
on the spot whether chest pain is being caused by a heart attack
or a more benign problem, saving time and potentially lowering treatment
costs substantially."
The team's discovery that DNA and proteins will bend tiny silicon
structures such as cantilevers has much wider implications, and
could make it possible to extend the technology to the operation
of micro- and nano-robotic machinery.
"Microbots and nanobots have been popularized in recent science-fiction
stories and movies, but technological issues remain an obstacle
to their realization," said James Gimzewski of IBM Research.
"The ability to use biology to perform specific mechanical
tasks on the nanometer scale with silicon provides a completely
new approach to operate machinery autonomously, without external
power or computer control. We have found a way to get DNA to do
the work for us, so we don't need batteries, motors, or the like
to operate tiny machines."
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Experimental setup of the biosensor in the laboratory. |
The ability of DNA and other biomolecules to operate machinery
such as valves using the molecules' specific code or biochemistry
could have applications in medicine. "For instance, we can
envision a system to attack cancerous growth: the release of just
the proper doses of chemicals in the appropriate location of the
body could be achieved using tiny microcapsules equipped with nano-valves,"
said Gimzewski. "They could be programmed chemically to open
only when they get biochemical signals from a targeted tumor type.
This would enable the right therapy at the right place at the right
time, with minimized side effects and no invasive surgery."
The technology underlying this new advance springs from development
work on nanomechanical olfactory sensors, as pursued by the research
teams at IBM in Zurich and at the University
of Basel. To date, applications of this work are mainly in quality
and process control, where the technology is used in sensing devices
for gaseous analytes, such as process gases or solvent vapors. Such
devices are not limited to gaseous environments, but also function
in liquids. This led the way to the research now reported in Science
on using the biomechanical sensors in biochemistry and medical diagnostics.
Technical background
The method is based on directly transforming specific biochemical
recognition into a nanomechanical motion. To do this, the researchers
used hybridization, the base pairing between two single strands
of DNA that results in the well-known double-helix structure. Hybridization
is a prominent example of molecular recognition.
The core of the device is an array of silicon cantilevers, each
500 microns long, 100 microns wide and less than 1 micron thick.
Each cantilever is coated on one side by specific biomolecules.
When immersed in solution, molecules of an injected substance dock
to a layer of receptor molecules that have been attached to one
side of the cantilever. Sensitizing an array of cantilevers, each
with a different receptor, allows docking of different substances
in the same solution. The increase of the molecular "packing
density" leads to surface stress and thus to bending of the
cantilever.
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Core of the instrument is the liquid cell in which
the cantilevers are mounted. |
The bending is of the order of 10-20 nanometers, which can be measured
accurately by well-established methods, such as laser beam deflection.
The hybridization was done with short strands of single-stranded
DNA (12mer oligonucleotides) and proteins known to recognize antibodies
of various mammals.
The scientific report on this work has been published in Science,
Vol. 288, Number 5464, April 14, 2000. The authors of the report
"Translating Biomolecular Recognition into Nanomechanics"
are Jürgen Fritz, Marko Baller, Hans Peter Lang, Ernst Meyer and
Hans-Joachim Güntherodt of the University of Basel, and Hugo Rothuizen,
Peter Vettiger, Christoph Gerber, and James Gimzewski of IBM Research - Zurich.
The work was partially funded by research programs of the Swiss
Government (MINAST—Micro and Nanosystems Technology—and
TOP
NANO 21*) for micro- and nanosystems.
More images are available on the web site of the
University of Basel.
*TOP
NANO 21 focuses on strengthening the Swiss economy through the
development and application of new technologies based on the NANOMETER.
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