The most advanced
scientific tool in development in UC Berkeley's department of bioengineering
is a microscope. Of course, this isn't just any microscope - this
microscope fits on the head of a pin. And someday this micro-microscope,
called a nanoscopic micro-CIA (microscale confocal imaging array),
could turn a PalmPilot into a portable biowarfare detection device
that can identify the slightest amount of biological warfare agents.
Or transform a microchip into an entire genomics or proteomics laboratory-on-a-chip
to study genes and proteins in the quest for new disease-fighting
drugs. Or enable physicians to monitor their patients' health, down
to a cellular level, from anywhere.
The nanoscopic micro-CIA is part of a large class of devices known as BioPOEMS (Bio-Polymer Opto Electro Mechanical Systems) invented by assistant professor of bioengineering Luke Lee. BioPOEMS merge the tiny machines of microelectromechanical systems (MEMS) with the world's smallest lasers, lenses, and plumbing. Fabricated by micromachining silicon or polymers in much the same way microchips are produced, BioPOEMS could ultimately cost only a few cents each when manufactured in large quantities.
"We want to use these as diagnostic tools for many applications, not just to detect biowarfare pathogens," Lee says. "They could have a huge impact on the future of preventive medicine."
A single nanoscopic micro-CIA is essentially a massively scaled-down confocal microscope - a $500,000 photocopier-sized tool used to study cellular mechanisms. Confocal microscopes work by shining a laser at a molecule that has been tagged with a fluorescent die. The laser "excites" the fluorescent molecule so it emits a specific color of light. In order to create a clear image of the sample, only one tiny point of the sample is illuminated at any moment. The laser scans the sample many times a second, imaging each tiny point, and a complete three-dimensional image is built.
Inside the nanoscopic micro-CIA, the sample molecules or cells travel through a system of channels and reservoirs etched in the polymer or silicon microsystem where they can be highlighted with fluorescent tags or mixed with other materials to analyze chemical reactions. Then, the molecules or cells flow under the lens of the microscope where they are illuminated with a laser diode.
Peg Skorpinski photo
Luke Lee, who immigrated to the United States from Korea when he was eighteen and lived in government housing, has a special interest in mentoring economically-disadvantaged minority students. The diverse student population at UC Berkeley, he says, is what kept him on campus as a faculty member after he received his PhD in 2000.
(Click for larger image.)
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In order to keep the light source tightly focused, a precise system of micro-lenses is necessary. And in the case of the nanoscopic micro-CIA and other BioPOEMS, it's no easy task to fabricate a lens as small as a few microns in diameter, twenty times thinner than a human hair. To do it, Lee and his team use a tiny drop of polymer that hardens when exposed to ultraviolet light. The tough part is focusing the lens. One way, Lee explains, is to confine the liquid polymer to a small area by surrounding it with water-resistant material that controls the shape of the lens. The lens can also be focused by applying a small voltage to change its surface tension, the tendency of the liquid to spread. Another method is to mount a pre-hardened lens on a micromechanical platform that moves up and down, much like a simple desktop microscope is focused.
With either solution, a series of rapidly moving mirrors inside the nanoscopic micro-CIA enables the beam to scan over the sample bit by bit just as with a full-size confocal microscope. Meanwhile, sensors act as eyes, looking for fluorescence and feeding that data to the computer controlling the nanoscopic micro-CIA. By analyzing that information, the computer can automatically detect and identify a single biomolecule.
So far, Lee has tested several separate elements of the nanoscopic micro-CIA but has not integrated all of the components into a fully-functional device. For instance, his latest micro-optical scanning design operates in only two dimensions. Still, that's more than enough, he says, to detect biowarfare agents.
Indeed, he believes that in three to five years his nanoscopic micro-CIA, funded by the Defense Advanced Research Projects Agency, could lead to an extremely sensitive wristwatch biomonitor that soldiers could wear. Via wireless radio links, physicians could keep tabs on an individual's physiology on a cellular and molecular level as well as identify any substance the soldier encounters.
Beyond the military applications, Lee lists a host of other uses for the nanoscopic micro-CIA and other BioPOEMS. Their price and size, he says, could enable pharmaceutical companies to develop new drugs by using incredibly efficient arrays of thousands of the nanoscopic micro-CIAs to study how different biomolecules interact.
Indeed, so-called "Labs on a Chip" are one of the hottest fields of bioengineering research. But Lee's long-term goals are even bigger feats. For one, he believes the optical qualities of the BioPOEMS could lead to neuroprosthetic retinas, bringing sight to the blind.
He'd also like to outfit a medical catheter with a nanoscopic micro-CIA, enabling the catheter to analyze the condition of cells on site. A physician could then conduct minimally-invasive but extremely high-resolution internal examinations. Then comes the next step.
"Once you can see what's going on inside the body on a single cell level, you could, for example, characterize a specific area as being cancerous," he says. "Then, perhaps you could use a laser tool along with the BioPOEMS to do true microscopic surgery."
Luke Lee's home page
BioPOEMS group
