Diagnosis On A Chip
by David Pescovitz
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Bernhard Boser holds an ImmunoSensor chip. The chips
are donated by National Semiconductor and then modified in UC
Berkeley's Microfabrication Laboratory. (David Pescovitz
photo)
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Beginning next
summer, a tiny bio-chip developed at UC Berkeley will help
researchers in Nicaragua understand and screen for a tropical
disease that incapacitates as many as 100 million people each year.
Melding microbiology with microcircuitry, the 2 millimeter square
ImmunoSensor provides a quick, inexpensive test for the dengue
virus, commonly known as "break-bone fever," even when the nearest
clinical laboratory may be hundreds of miles away.
"In the
third world, there aren't very many specialized labs that can test
these blood samples," says co-inventor Bernhard E. Boser, a
professor in the Department of Electrical Engineering and Computer
Sciences and a researcher with the Center for Information Technology
Research in the Interest of Society (CITRIS). "Many regions don't
even have the quality of water you need to do traditional
tests."
The solution was to put the laboratory right on the
chip, at a cost of less than $1 each. In fact, right now Boser and
his collaborators--Molecular and Cell Biology professor P. Robert
Beatty, professor Eva Harris in the School of Public Health, and
their graduate students--are readying 1,000 of the ImmunoSensors to
ship to Nicaragua in time for dengue season. Spread by mosquito, the
dengue virus causes brutal headaches, intense fever, rashes, and, in
infants, the risk of death. The field study is being coordinated by
the Sustainable Sciences Institute (SSI), a non-profit organization
focused on addressing local problems related to infectious diseases
in developing nations.
Each ImmunoSensor chip is fabricated using bulk
processes similar to the way integrated circuits are
manufactured. (courtesy the researchers)
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Currently,
diseases like the dengue virus are detected with a test called the
Enzyme-Linked Immunosorbent Assay (ELISA), which detects antigens
and antibodies in a blood sample. Antibodies are formed by the body
in response to antigens -- molecules, often foreign, that the immune
system recognizes as threats. For every antigen, there is an
antibody that binds to it. It's this biochemical reaction that
signals the immune system to start fighting off a disease. With
ELISA, an enzyme is added to the sample that activates a visible
colored dye in the presence of a particular antigen or antibody.
In lieu of messy enzymes and dyes, the ImmunoSensor employs
magnetism and microelectronics. (See illustration.) First, a drop of
blood is placed in a micron-scale well on the chip. There, it mixes
with tiny micron-scale magnetic beads that are pre-coated with an
antibody that bonds to the antigen indicative of a particular
disease.
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This illustration depicts the how
antigens bind to both the magnetic beads and the
magnetic sensors, called Hall sensors, on the surface of
the chip. (courtesy the researchers)
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"If the
antigens are in the blood sample, the beads grab onto them," Boser
explains.
Then, gravity causes the beads to fall onto a tiny
array of 256 magnetic sensors at the bottom of the well. The sensor
array is also coated with the particular antibody that binds to the
disease antigen. After the beads settle, a magnetic field is
applied. Beads that aren't now immobilized by the antigen on the
surface of the chip are pulled away from the sensor array.
"We call it magnetic washing," Boser says.
Finally,
the sensor array is activated. The electrical resistance of the
array corresponds to the number of beads that are stuck on the
sensors thanks to the antibody-antigen bond. The detection of
immobilized beads mean the particular antigen is present and that
the subject whose blood was tested most likely is infected with the
dengue virus. The entire process takes little more than a
minute.
Currently, the chip plugs
into a conventional laptop computer running the ImmunoSensor
software that provides the data to the person administering the
test. The next step, Boser says, is to make the chips wireless and
port the software over to a palm computing platform, even further
increasing their portability. Meanwhile, Beatty is working to
develop an HIV test that would also run on the ImmunoSensor
platform.
"You could imagine buckets of these chips, all
coated with different antibodies so we can not only detect
on-the-spot when someone is ill, but also find out exactly what
illness they have," Boser says.
Bernhard E. Boser's Home Page
Center for
Information Technology Research in the Interest of
Society
Sustainable Sciences Institute
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2003 UC Regents. Updated 9/29/03.
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