May 2002

Nanobiotech Makes the Diagnosis

Electronic components the size of molecules could test for diseases and provide personal DNA profiles on demand.

By Alexandra Stikeman

Gazing at an electrical meter, Yi Cui, a graduate student in the Harvard University lab of chemist Charles Lieber, waits for evidence of a remarkable feat in simple, ultrasensitive diagnostics. His target is prostate cancer. His new tool is a microchip bearing 10 silicon wires, each just 10 nanometers (billionths of a meter) wide. These nanowires have been slathered with biological molecules with an affinity for PSA, a protein all too familiar to men of a certain age as the telltale sign of prostate cancer. If the experiment works according to plan, when the PSA molecules bind to the nanowires, there will be a detectable electrical signal.

Cui washes a solution containing prostate cancer proteins over the chip. Immediately, the meter registers subtle changes, indicating not only that the device has detected the protein, but that it detected perhaps as few as three or four molecules, instantly and with minimal sample preparation-a previously unheard-of feat. The implications for diagnostics are enormous. A successful prostate cancer test must distinguish between normal and elevated protein levels. Ultrasensitive sensors like Lieber's could discern the slightest increase; what's more, they could do so in cheap, disposable tests that patients could use at home between visits to the doctor. "If I were at risk for a particular cancer, I wouldn't want to take a chance and wait for some cancer cells to grow wildly out of control over a year because the previous test missed it," says Lieber.

Though this nanowire device is just an experimental prototype, it is at the forefront of a growing effort at labs around the world to marry nanoelectronics and biology into a new field called nanobiotechnology. This hybrid discipline is producing a variety of tools-from arrays of tiny sensors that can detect specific biological molecules to microscopic systems carved out of silicon that can read individual strands of DNA-capable of providing a new window on biological molecules.

The implications for medicine and biotechnology are myriad. Besides sniffing out the barest whiffs of disease-or perhaps detecting a single spore of anthrax-these devices could provide far faster and easier diagnosis of complex diseases. For example, they could provide early warnings about heart attacks, whose calling cards are subtle changes in the mix of dozens of proteins. Alternatively, a single microchip could provide a comprehensive diagnosis from a drop of blood. And for drug researchers, nanobiotech gadgets could mean new tools for discovering and evaluating potential drugs more rapidly, by screening millions of different drug candidates at once. Some of these more ambitious goals will likely take years to achieve, but nanobiotech could lead to real devices that will begin replacing cumbersome lab-based procedures with cheap, accurate microchips in as little as two years.

These first products-chips rigged to detect a specific disease or cluster of genetic disorders-are already being developed at nearly a dozen nanobiotech startups (see " Sensing Success ") . Larry Bock, CEO of Palo Alto, CA-based startup Nanosys [ TR board member Robert Metcalfe is a Nanosys cofounder and director. Ed.], which has licensed Lieber's technology, predicts his company will market a commercial sensor within three years, first for use as a research aid to rapidly screen potential drugs, and later as a cheap, disposable at-home test for prostate cancer and perhaps other cancers. "People talk about all the wonders of nanotechnology but then say it's not going to happen for another 20 years," says Chad Mirkin, a chemist and director of the Institute for Nanotechnology at Northwestern University. "But that's absolutely incorrect for things like diagnostics. You're going to see products on the market in the next two years."