TINY springboards carved out of silicon can act as a sensitive detector for
prostate cancer, the most common form of cancer in men. The research team
developing the detector say this is the first time microscopic structures have
been used to make accurate measurements of levels of clinically important
molecules.
鈥淭his opens up new possibilities for sensitive screening for cancer-related
proteins and eventually rapid testing in protein chips,鈥 says team member Arun
Majumdar of the University of California, Berkeley.
Working with Thomas Thundat of Oak Ridge National Laboratory in Tennessee and
cancer researcher Richard Cote at the University of Southern California in Los
Angeles, Majumdar used standard semiconductor fabrication techniques to forge a
triangular silicon nitride cantilever a mere 200 micrometres long
(see Diagram).
They then studded the upper surface of the cantilever with antibodies that bind
to a protein called prostate specific antigen (PSA), which is shed into the
bloodstream by prostate tumours.
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When the researchers flushed a solution containing PSA over the cantilever,
they found that it bent slightly as the protein molecules bound to it. It wasn鈥檛
the weight of the extra molecules that moved the cantilever: there were far too
few of them for that. Instead, as the PSA molecules pack onto the surface of the
silicon they change the stresses in the surface, and this is what makes the
cantilever bend.
The bending was detected by bouncing light from a low-power laser off the
cantilever. The researchers could detect movement of less than 10 nanometres,
about the width of a hundred hydrogen molecules.
Majumdar and his team detected PSA at levels down to 0.2 nanograms per
millilitre. This is already as sensitive as the ELISA assay commonly used for
PSA, and the researchers hope to improve on this by making the cantilevers
longer. They say that a mass-produced version of the cantilever system could
eventually make testing for prostate cancer cheap and routine.
However, there are some important obstacles to overcome before this can
happen. One problem is the bulky laser, which could possibly be replaced with
cheap LEDs. Alternatively, the binding PSA molecules could be detected by a
change in electrical resistance.
Another problem is that changes in temperature and acidity can also make the
cantilever move. The researchers plan to get round this by creating rows of
identical cantilevers, coating just one of them with antibodies and using the
others as controls.
James Gimzewski at the University of California in Los Angeles says his group
has already produced arrays of cantilevers. He is working with a company that
makes atomic force microscopes to produce a cantilever system for detecting
defects in strands of DNA. 鈥淵ou can translate any biochemical or chemical
interaction into a cantilever motion,鈥 says Gimzewski. 鈥淚t is an incredibly
powerful technique.鈥
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More at:
Nature Biotechnology (vol 19, p 856)