A Liquid Asset

The ease of integrating the silicon detector with other components should make it useful in microfluidics, a hot area of biomedical research. In microfluidics, the various steps involved in preparing and testing a sample are executed on a microchip. The liquid in, say, a blood sample moves through microscopic channels, where procedures such as bursting open cells, separating their component molecules, and running tests on those molecules all happen in tiny channels.

Manalis says the silicon microchannels built by his lab can be easily incorporated into such a microfluidic scheme. His detectors, he points out, determine the contents of an extremely small volume of liquid, about 10 picoliters – roughly the volume of a single cell.

Other physicists have shown that microscopic vibrating cantilevers could be an extremely sensitive method for detecting mass, explains Manalis. “If you talk to physicists, their favorite quantity to measure is vibrational frequency because it is very easy to measure. It’s very robust, and it is very hard to interfere with.”

But previous work had encountered a seemingly insurmountable practical problem when it came to detecting biomolecules: the cantilevers had to operate in a dry environment, preferably in a vacuum. In water or any other liquid, the delicate vibrations would be instantly damped. That’s a problem, says Manalis, because the biomolecules that scientists want to detect – viruses, for example – are found in aqueous environments, such as a blood sample. In biology, he points out, “everything happens wet.”

It is here that Manalis came up with an ingenious solution. He and his colleagues hollowed out a tiny channel inside the cantilever so that small volumes of the sample would flow into it; the targeted biomolecules bind to the inner walls. The vibrations of the suspended resonator are still affected by the mass of the binding molecules, but there is no longer any surrounding fluid to damp them.