Bioagent Chip Source: Scientific American Speed is of the essence in successfully containing a
biological warfare attack. Quickly identifying the agent and how to
treat those who have been exposed are keys to controlling an outbreak
and minimizing its destructiveness. A handheld device containing a
laboratory-on-a-chip may just be the answer. The result of
breakthroughs in biology, chemistry and
micromanufacturing, the instrument can immediately alert investigators
to even the slightest hint of anthrax or smallpox in the air.
Although there are myriad proposals for building these
biosensors, the double whammy of identifying a particular bioagent in
less than two minutes, and doing so given a sample of only a few
cells, has been difficult to achieve. "There are many diseases that
are as effective as inžuenza--they can affect you at the single- or a
few-particle level," says Mark A.
Hollis, manager of the biosensor technologies group at the
Massachusetts Institute of Technology Lincoln Laboratory, where a
collaborative effort with M.I.T. biologist Jianzhu Chen and his
colleagues hopes to deliver a prototype biosensor in less than 18
months. The work is part of the Defense Advanced
Research Projects Agency's four-year, $24-million Tissue Based
Biosensors program, which funds research by about a dozen universities
and private firms.
Mouse B cells power the device. Part of the immune
system, B cells express antibodies on their surfaces that bind to
particular infectious particles. For example, most humans harbor B
cells for pathogens that cause colds, polio, tetanus and other
diseases. When a B cell binds to the intruder that
it is built to recognize, a biochemical cascade occurs in the cell,
triggering the body's immune system to rally to the defense. "We're
leveraging off probably 600 to 800 million years of genetic
engineering that nature has already done to recognize an infectious
agent," Hollis observes.
With the design legwork out of the way courtesy of basic
biology, Hollis's colleagues genetically engineer the B cells to
respond to particular biowarfare agents. To know that the B cells have
actually gone into action, the researchers plug into B cells another
gene--from a jellyfish called Aequorea. This gene enables the
jellyfish to glow with the bioluminescent
protein aequorin. The aequorin instantly emits light when triggered by
calcium ions--a substance that is produced when the bioagent-induced
cascade occurs in the B cell. The entire process, from detection to
bioluminescence, takes less than a second, beating any human handiwork
to date.
Other methods have matched either the speed or the
sensitivity of the B cells, but not both. The record for analyses
using the polymerase chain reaction of a bioagent, Hollis says, is
about 12 minutes, based on a pristine sample containing more than 20
organisms. Immunoassay techniques, which also use an antibody-capture
methodology, are approaching the
requisite speed but lack sensitivity: a sample containing at least
several thousand copies of the organism is needed to identify an
agent. In contrast, "only one infectious particle is sufficient to
trigger a B cell because that's the way nature designed it," Hollis
notes. "It's a beautifully sensitive system."
Currently the biosensor is a 25-millimeter-square
plastic chip that has a meandering žow line running through it. One-
to two-millimeter-square patches, containing 10,000 B cells engineered
for an individual agent, line the surface of the channel. A strict
diet combined with a room-temperature climate keeps the cells in their
place by naturally discouraging cell
division. Even hungry and cold, they stick to the task at hand.
Elegant microžuidics, also developed at Lincoln, direct
the sample and nutrient media through the channel, where a
charge-coupled device (CCD) like those found in camcorders detects
even a single B cell firing. Identification based on five to 10
particles per sample has been demonstrated, and Hollis expects no
problems detecting deadly bioagent particles in even the smallest
numbers.
The biosensor, too, is naturally robust: exhaust, dirt
and other contaminants that make the working environment considerably
less than hospitable, compared with a B cell's traditional home inside
the body, don't trick the cells into misfiring. "There's a lot of
stuff in your blood, and these things are designed not to respond to
any of it other than the
virus they're intended for," remarks Hollis, who points out that the
same B-cell-based biosensing technology developed for military use
could be employed for instant viral identification in a doctor's
office.
The last big question on Hollis's research
agenda--whether the cells will reset after having fired--may not even
matter in the group's latest vision for a handheld biosensor: a
proposed optical-electronic box would read the photons emitted by a
swappable and disposable biosensor chip, which would cost just a few
dollars. "If you are hit with a biological attack,"
Hollis says, "you'll probably want to take the chip out and send it
off to Washington for confirmation." Probably so.
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DAVID PESCOVITZ (david@pesco.net) is based in Oakland,
Calif. He is a contributing editor at Wired and I.D. magazines.
by David Pescovitz
http://www.sciam.com/2000/0300issue/0300techbus4.html