Diagnosis On A Chip
by David Pescovitz
 Printer-friendly
version
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)
|
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)
|
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.
 |
|
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) |
|
"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
Lab Notes is
published online by the Public Affairs Office of the UC Berkeley
College of Engineering. The Lab Notes mission is to illuminate groundbreaking
research underway today at the College of Engineering that will
dramatically change our lives tomorrow.
Media contact: Teresa
Moore, Lab Notes editor, Director of Public Affairs
Writer, Researcher: David
Pescovitz
Web Manager: Michele
Foley
Subscribe or send comments to the Engineering Public Affairs
Office: lab-notes@coe.berkeley.edu.
© 2003 UC Regents.
Updated 9/29/03.
|
