science-fiction fantasy of nanotechnology building
novel structures, devices, and materials at the atomic
or molecular scale is becoming a reality. For the
great potential of nanoscience and nanotechnology to be
fully realized, however, research efforts must cross many
disciplines, from electrical engineering, mechanical engineering,
materials science, and computer science to bioengineering,
chemistry, and physics.
is this cross-disciplinary approach fostered more than
at UC Berkeley. Each month, Lab Notes is proud
to present the work of nanotechnology researchers from
the College of Engineering and our collaborators across
by David Pescovitz
The Book of Life is now open in front of us in the form of our genetic code. But
for the Human Genome Project to live up to its potential in the
fight against disease, we must understand the proteins encoded by
the genome, an endeavor known as proteomics.
this illustration, the cantilever on the left bends as PSAs
(prostate cancer markers) bind to it. The other cantilevers
remain straight because the molecules they're exposed to
are not PSAs. The laser measures the deflection of each
courtesy Kenneth Hsu/UC Berkeley & the Protein Data Bank
"As mechanical engineers, we're tackling proteomics through the mechanics of molecules," says Mechanical Engineering professor Arun Majumdar.
And so far, this unique approach has paid off. The researchers'
biochemo-optomechanical (BioCOM) chip uses an array of diving
board-like cantilevers that bend in the presence of proteins characteristic
of prostate cancer, the No. 2 killer of men in this country. Thanks
to its innovative engineering, the BioCOM detects the prostate-specific
antigens (PSAs) at levels 20 times less than necessary to catch
the cancer in its earliest stages. Eventually, the cantilever
approach could lead to a drug discovery chip with the ability
to analyze thousands of compounds, highlighting those that may
be useful weapons against a specific disease.
"In this post-genomic era, the high-throughput analysis of proteins and nucleic acids is of primary importance," Majumdar says. "This could lead to fast screening and molecular profiling for many diseases and a possible cancer chip for detecting cancer."
The BioCOM is
one of several UC Berkeley projects at the intersection of nanotechnology
and MEMS, micro-electromechanical systems being mass manufactured
in a process similar to the way microchips are made.
"We are bridging the length scale between the nanoscale and the microscale," says Majumdar, who collaborated on the project with graduate students and researchers from Berkeley, USC and Oak Ridge National Laboratory.
The BioCOM's silicon nitride cantilevers, each half the width of a human hair,
are coated with certain antibodies that only bind to specific
proteins, for example, PSAs. As the proteins bind to the cantilevers, they
push and pull to make room for each other. This change in conformation
causes the cantilever to bend. A laser measures this deflection,
which may only be a few nanometers depending on the amount of
protein in the sample.
"You have to be quantitative," Majumdar says. "It is the balance of the protein in your cell, its expression, that determines if the cell is cancerous or diseased in some other way."
scanning thermal electron microscope, the most advanced
of its kind, will enable Arun Majumdar to create three-dimensional
thermal maps of transistors and other miniature devices.
(Click for larger image.)
Traditional "one analyte at a time" assays require molecules to be flagged with fluorescent tags for identification, a problem in drug discovery as the similarity in size between the drug molecule and the tag may inhibit binding. Majumdar's mechanical approach negates the need for tags while enabling samples to be processed en masse.
"If you have an array of thousands of pixels, you can functionalize each pixel with molecules from drug libraries to see what candidate drugs bind to which target," Majumdar says.
The BioCOM is only one of several innovative projects in
Majumdar's Nanoengineering Laboratory. His group is also studying
the thermal conductivity of nanowire arrays grown by researchers
in Berkeley's College of Chemistry. Understanding heat transport
in nanowire arrays could lead to tiny solid-state refrigerators
to cool high-performance microprocessors or thermoelectric devices
that convert waste heat into power. And in another bio-nano effort,
Majumdar is looking at how complementary strands of DNA might be
used as transports and glue for assembling inorganic nanoparticles
into desired patterns. Once the nanoparticles are properly connected,
the DNA is burned off.
"We are not only looking at how mechanical engineering can help
biology, but at how biology can help us," Majumdar says. "The
biological toolbox is already there; we just have to learn how
to use it."
Majumdar's home page
Berkeley Nano-Engineering Laboratory
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