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SCIENCE AND TECHNOLOGY |
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"Serum proteins provide an incredible window into the biology of disease," says Paul Mischel, a professor of pathology at the University of California, Los Angeles. The current method for getting blood work done involves a doctor or nurse drawing 10 to 15 milliliters of blood into several vials, multiple technicians analyzing that blood for many hours, and an end cost of about $500 per test. With
that in mind, how does this sound? A new chip can do the same work in 10
minutes with one drop of blood. "We
decided to make things dirt cheap: it costs a nickel a protein," Heath
says of the current device. The microfluidic chip is being developed by James Heath, a chemistry professor at Caltech, and Institute for Systems Biology founder Leroy Hood. The chip performs the entire test, separating cells and proteins, and tagging the proteins so that they'll light up under a microscope if anything is found. The technology, they say, will make it possible for doctors to give a bedside diagnosis based on blood analysis, rather than having to wait a week. Even better, it analyzes blood when it's fresh, rather than letting the quality of the sample degrade, making it far more accurate. Such rapid and cheap tests requiring only a drop of blood should allow doctors to monitor more proteins more frequently, enabling earlier detection of diseases like cancer and better preventive care for the elderly. Katherine
Bourzac writes in the Technology Review: Heath
and Hood's device, described in this week's issue of Nature
Biotechnology,
starts the analysis process with some simple microfluidics. A drop of blood is
pulled down a microscale channel by the application of a small external
pressure. This first channel branches off into narrower ones, which exclude
blood cells and admit the protein-rich blood serum. In typical blood tests,
this separation step requires a centrifuge. The
narrower channels are patterned with what Heath calls a protein bar
code--lines of DNA bound to antibodies that capture proteins of interest from
the serum. After the serum and cells are flushed out, antibodies bound to red
fluorescent proteins are flushed in, lighting up captured blood proteins. The
protein bar codes can be read under a fluorescent microscope or a gene-chip
scanner. The identity of the captured blood proteins can be determined by the
location of red lines in the bar code relative to a green fluorescent
reference line. By
measuring how much light radiates from a particular protein's spot in the bar
code, Heath and Hood can quantify its concentration in the blood. Heath notes
that the chip can measure blood proteins present over a wide concentration
range, making it possible to measure not only plentiful blood proteins created
by the immune system, but also rarer proteins originating in organs such as
the brain. The device is as sensitive as conventional protein tests, and Heath
and Hood can measure any proteins they're interested in by making custom chips
with the right antibodies. While
other groups have focused on proteins that are created by many organs, making
the results difficult to interpret, Hood says, "We're developing a
strategy to identify blood proteins that are organ-specific." Hood says
his group is currently using mass spectrometry to discover proteins specific
to the liver and brain. In
their published paper, the researchers describe using the blood test to
determine the risk level of people with breast and prostate cancer. Heath says
that the chip is being tested in clinical trials involving both cancer
patients and healthy individuals. The studies of healthy patients that the
group is currently undertaking would be impractical using technologies that
require a large blood draw, but using the chips, Heath says that it's possible
to measure blood proteins several times a day. The researchers are using the
blood chips to monitor how diet and exercise influence blood-protein
composition. "These devices should lead to a decrease in cost and an incredible benefit to patients," says Emil Kartalov, a professor of pathology at the University of Southern California's Keck School of Medicine. Kartalov, who's not collaborating with Heath and Hood, is developing similar chips, and he developed some of the separation methods used on the blood chip. Kartalov says that Heath and Hood's work is a major step forward, but that for these chips to truly go out into the field, they'll need to move beyond fluorescent proteins. Fluorescent microscopes are too expensive and too bulky to be carried onto the battlefield or into patients' homes. Kartalov says that future diagnostics will probably replace the fluorescent proteins with charged proteins, since measuring changes in electrical current is much simpler and more practical. |
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