May 2002

Nanobiotech Makes the Diagnosis

Continued from page 1

By Alexandra Stikeman

Power in Numbers

Biology and electronics have long existed in separate universes. But because biological molecules, like DNA and proteins, are roughly a few nanometers in size, and because physicists and chemists are now learning how to make electronic devices on exactly that size scale, these universes are colliding. The result is a new class of devices that combine the ability of biological molecules to selectively bind with other molecules with the ability of nanoelectronics to instantly detect the slight electrical changes caused by such binding. "What's really interesting about this technology is that it allows one to take the inorganic components that normally would be nestled inside an electrical chip and combine them with biological molecules," says Paul Alivisatos, scientific cofounder of Nanosys and a chemist at the University of California, Berkeley.

Indeed, nanoelectronic devices like the one built in Lieber's lab (see " Sensitive Wire ") could do away with the elaborate apparatus now needed for ultrasensitive detection. "If you wanted to do single-molecule detection in a lab today, you would need a laser the length of a desk and a lot of sophisticated optics, chemical labels to amplify the signal enough to be able to see it," Bock says.

Shrinking down such ultrasensitive devices enough that they could be put on chips could have numerous applications in diagnostics. Stanford University chemist Hongjie Dai, for example, has built a device that can detect glucose with a single carbon nanotube, a large carbon molecule with excellent electrical properties (see " The Nanotube Computer ," TR March 2002) . The glucose molecules react with molecules on the surface of the nanotube, creating electrical signals that correspond to glucose concentrations, he says. Though only a proof of concept today, such a device could be developed into an implantable glucose sensor for diabetics. In December, Dai launched Molecular Nanosystems in Palo Alto, CA, to commercialize nanotube-based devices including biosensors.

For many applications, though, what's really needed is not a lone nano detector but a dense array of them. That way, you can rapidly look for thousands, even millions, of different biological molecules in a single drop of blood or other body fluid, allowing the diagnosis of diseases that have complex molecular signatures. One such disease is rheumatoid arthritis-an autoimmune disease with many variants, each marked by subtle differences in groups of proteins. Ideally, each variant would be fought with a slightly different treatment; in practice, sufferers today are generally treated in the same way. But, says Dai, a nano array could serve as a highly precise and discriminating diagnostic device, providing a road map for custom treatment.

These arrays of nano detectors promise advantages over existing technologies, like DNA chips, and ones under development, like protein chips. All such chips require fluorescent labeling of molecules and optical microscopes to detect the glow given off when binding occurs (see " DNA Chips Target Cancer ," TR July/ August 2001) . What's more, roughly a thousand molecules must bind to each sensing element to create the glow. With nanoelectronics, no bulky, expensive equipment is needed, and instant detection of just a few molecules is possible.

Sensitive Wire

To detect a disease-related protein in a blood sample, a silicon wire just 10 nanometers wide is coated with biomolecules that bind only to that protein (below). When the disease protein binds to a molecule on the wire (inset), the wire's conductance changes, providing an instant electric signal.