Biochips can detect cancers before symptoms develop
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ARGONNE, Ill. (May 9, 2008) — In their fight against cancer, doctors
have just gained an impressive new weapon to add to their arsenal. Researchers
at the U.S. Department of Energy's Argonne National Laboratory have developed
a chip that can save lives by diagnosing certain cancers even before patients
become symptomatic.
The new technology, known as a biochip, consists of a one-centimeter by one
centimeter array that comprises anywhere between several dozen and several
hundred "dots," or small drops. Each of these drops contains a unique
protein, antibody or nucleic acid that will attach to a particular DNA sequence
or antigen.
A tumor, even in its earliest asymptomatic phases, can slough off proteins
that find their way into a patient's circulatory system. These proteins trigger
the immune system to kick into gear, producing antibodies that regulate which
proteins belong and which do not.
"Antibodies are the guardians of what goes on in the body," said
Tim Barder, president of Eprogen,
Inc., which has licensed Argonne's biochip
technology to search for new biomarkers that indicate cancer. "If a cancer
cell produces aberrant proteins, then it's very likely that the patient will
have an antibody profile that differs from that of a healthy person. You can
look for similarities and differences in autoantibody profiles to look for
clues and markers that provide early indicators of disease."
In their hunt for cancer indicators, Eprogen uses a process called 2-dimesional
protein fractionation, which sorts thousands of different proteins from cancer
cells by both their electrical charge and their hydrophobicity or "stickiness."
The 2-D fractionation process creates 960 separate protein fractions, which
are then arranged in a single biochip containing 96-well grids. Eprogen scientists
then probe the microarrays with known serum or plasma "auto-antibodies" produced
by the immune systems of cancer patients.
By using cancer patients' own auto-antibodies as a diagnostic tool, doctors
could potentially tailor treatments based on their personal autoantibody profile. "This
technology is really designed to take advantage of the information contained
within the patient's own biology," Barder said. "What makes this
technique unique is that scientists can use the actual expression of the patient's
disease as a means of obtaining new and better diagnostic information that
doctors could use to understand and fight cancer better.
"We're starting to see a way of developing tests and therapies
for cancer by bringing the bedside to the laboratory, rather than the other
way around," he added.
Biochips have already shown promise in diagnostic medicine, according to Argonne
biologist Daniel Schabacker, who developed the technology. In addition to Eprogen,
three other companies have licensed biochips, he said. One of these companies,
Akonni Biosystems of Frederick, Md., has already produced dozens of assays,
which it markets under the TruArray® brand name. Another company, Safeguard
Biosystems, licensed biochips for veterinary diagnostic applications.
When a biochip tailored to detect upper respiratory diseases is exposed to
a swab taken from a patient's mouth, for instance, the binding patterns of
the proteins or nucleic acids in the array cause the dots to "light up" when
scanned and analyzed with a computer. Computer algorithms decode the dot pattern
produced by the biochip, calculate the statistical likelihood of each possible
infection and provide this information to the doctor.
"Suppose someone shows up to the hospital and they're sick with an upper
respiratory infection," said Schabacker. "First thing a doctor is
going to want to know is whether the infection is viral or bacterial; this
is especially true in pediatrics. And ideally, they'd really like to have a
single test that they can run very rapidly that will identify exactly which
disease you have from a dozen top targets."
The development of products like TruArray will soon revolutionize doctors'
ability to quickly diagnose a number of diseases, Schabacker said. For example,
while existing rapid strep tests performed by many pediatricians take only
a few minutes to process, they yield so many false negatives that doctors routinely
send out the samples for subsequent rounds of more thorough, time-consuming
and expensive analysis.
"The unique advantage offered by the TruArray platform lies in the fact
that we can screen a single sample for multiple viral and bacterial infections
at the same time," said Charles Daitch, Akonni's president and CEO. "Soon,
doctors will no longer need to order as many expensive and time-consuming tests,
and can instead obtain accurate diagnoses that will enable them to quickly
provide their patients with targeted treatment strategies."
Though the analysis of a sample on a biochip can take 30 minutes, scientists
can have much more confidence in the accuracy of the diagnosis, according to
Schabacker. "Biochips give us the ability to run a test that allows your
doctor to figure out exactly what you're suffering from during the time that
you're in his or her office," he said.
While biochips will allow doctors
to more quickly and authoritatively explain your sniffles, they might also
be used for patients who exhibit symptoms of much more serious infections.
By adding just a few more drops to the chip's array, Schabacker claimed,
lab technicians could test for a whole slate of biotoxins and especially virulent
diseases from the plague to smallpox to anthrax.
Other infections, such as those caused by Multidrug-Resistant Tuberculosis
(MDR-TB) and the often deadly Methicillin-resistant Staphylococcus aureus (MRSA),
can be quickly diagnosed with biochips like Akonni's TruArray assay, according
to Daitch.
"The most important thing with these types of infections is that you
have to be right and get the answer quickly," Schabacker said. "Some
of the tests out there, though marginally quicker than ours, are so inaccurate
that they're almost useless. Especially when you're talking about anthrax or
plague, you have to be confident in your diagnosis or else risk causing a panic."
Argonne National Laboratory brings the world's brightest scientists and engineers
together to find exciting and creative new solutions to pressing national problems
in science and technology. The nation's first national laboratory, Argonne
conducts leading-edge basic and applied scientific research in virtually every
scientific discipline. Argonne researchers work closely with researchers from
hundreds of companies, universities, and federal, state and municipal agencies
to help them solve their specific problems, advance America 's scientific leadership
and prepare the nation for a better future. With employees from more than 60
nations, Argonne is managed by UChicago
Argonne, LLC for the U.S.
Department of Energy's Office
of Science.
By Jared Sagoff.
For more information, please contact Steve McGregor (630/252-5580
or media@anl.gov) at Argonne.
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