When doctors now test patients for disease markers such as prostate-specific antigen (PSA), a protein that can signal early prostate cancer, they often rely on an enzyme-linked immunosorbent assay, or ELISA test. But researchers at the University of California at Berkeley and Oak Ridge National Laboratories have created a new type of assay that they say may prove as sensitive and less expensive. The group, which describes their work in this month's issue of Nature Biotechnolgy, produced a micromachined cantilever¿essentially a tiny diving board¿that bends in response to protein markers at levels 20 times lower than what is needed for diagnostic purposes.
"This [device] offers the possibility of a common platform for high-throughput detection of proteins, DNA and/or RNA, in areas ranging from disease diagnosis to drug discovery," Arun Majumdar, a mechanical engineering professor at Berkeley, says. "This could lead to fast screening and molecular profiling for many diseases and a possible cancer chip for detecting cancer."
The researchers fashion the cantilevers¿which measure about 50 microns wide, 200 microns long and half a micron thick¿from silicon nitride using methods developed to create microprocessors. They then coat each cantilever with antibodies or single-strand DNA for genetic tests. When matching proteins or DNA bind to the coatings, the lever bends downward. A laser measures this movement, the extent of which gives some indication of how much protein or DNA has attached to the lever.
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In addition to its ability to gauge amounts, the device has other advantages over current methods: it can look for multiple markers in a single reaction and does not require the use of fluorescent tags. But according to Oak Ridge researcher Thomas Thundat, who first published the foundation of the idea in 1994, "the primary advantage of the microcantilever method originates from its sensitivity, based on the ability to detect cantilever motion with subnanometer precision, as well as the ease with which it may be fabricated into a multielement sensor array. No other sensor technology offers such versatility."
