New Single-Molecule Detector

Using tiny silicon rings that trap and circulate light, researchers have made an ultrasensitive device that can detect single biomolecules. Unlike standard techniques for detecting individual molecules, the new method, described online in Science last week, does not require labeling the target molecules with fluorescent tags, potentially making it simpler and less expensive.

Detecting individual biomolecules could provide an ultrasensitive and easy-to-use screen for protein biomarkers associated with cancer and a new way to analyze DNA molecules to identify genetic and infectious diseases. By sniffing out the telltale molecules even when they exist at very low concentrations, the detection method could help catch cancer in its very early stages and pathogens before they spread, says Kerry Vahala, an applied physics professor at the California Institute of Technology.

Most standard techniques to sense single molecules require tagging the target molecules with fluorescent chemicals. These fluorescent dyes shine when exposed to light so that researchers can spot the target molecules and measure their concentration. “You’re essentially putting a big neon sign on the molecule so that it lights up very brightly,” Vahala says. The method works well but requires extra processing steps and specialized lab equipment.

Instead, the new doughnut-shaped silicon detectors rely on measuring light frequency. The silicon rings, which average 80 micrometers in diameter, trap light of a particular resonance frequency. When a target molecule sticks to a ring, it slightly changes the frequency of the light.

Vahala and his colleagues make an array of the rings using common fabrication techniques. They coat the silicon surface with specific molecules that bind to the target molecules–for example, an antibody to an immune-system protein. Then the researchers immerse the detectors in water or human blood serum containing the protein, throw laser light on the setup, and monitor the light frequency with an optical detector. Every time a protein molecule lands on a silicon detector, the frequency changes.

“You could envision sets of rings that are prepared to look for different chemicals or biomolecules,” Vahala says.

The frequency change is easy to detect because the silicon rings trap light very effectively. “The light that’s trapped inside the doughnut will stay there for a long time, relatively speaking, for the time scale of light,” Vahala says. “It will stay there for hundreds of nanoseconds.” Light circles around the ring more than 100,000 times–thousands of times longer than in similar commercial devices–interacting with the protein at every pass. As a result, the frequency change gets amplified enough to be picked up easily. This approach to detecting the signal is new and “very exciting,” says Richard Zare, a chemistry professor at Stanford University.

Many researchers are developing methods to detect single biomolecules that do not require fluorescent tagging. But the new method is one of the first to detect single molecules using light, says Stephen Quake, a bioengineering professor at Stanford University. “It’s a real tour de force and will probably have tremendous applications in the sensing area,” he says.