Scott Manalis holds in his palm a thin microchip about the size of a fingernail. To the naked eye, it looks similar to the chips you might find in your cell phone or iPod. What’s different is buried in the chip and hidden from sight: a suspended vibrating microchannel carved out of silicon.
It is, says Manalis, “to our knowledge, the world’s most sensitive way to measure the mass of biomolecules or the mass of cells in an aqueous environment.”
Pointing to a micrograph showing a cross section of the chip, Manalis, who developed the sensor with then graduate student Thomas Burg, explains how the technology works. The key is the microchannel, which is 300 micrometers long, 50 micrometers wide, and a few micrometers thick. It acts like a tiny diving board; once its inner surface is chemically treated, specific proteins or other biomolecules selectively bind to it, and the added weight changes the frequency of its vibrations. That change, which can be measured either electronically or with a laser, corresponds directly with the mass of the binding molecules.
Manalis, a professor of biological and mechanical engineering at MIT’s Media Lab, believes the technology could provide not only an extremely sensitive but also a highly practical method for detecting everything from viruses to cells to protein biomarkers. Indeed, this fall Manalis received a five-year, $3.2 million grant from the National Cancer Institute to develop a sensor for sniffing out the rare proteins that can be the telltale signs of cancer. His first target: prostate cancer.
With standard techniques, detecting biomolecules generally requires labeling them with fluorescent tags. The glow of the tags can be measured with an optical reader to determine whether a particular molecule is present and, if so, in what quantities. This technology has become one of the workhorse tools of biotechnology and is used, for example, in DNA microarrays for genetic testing.
But fluorescence-based devices have two severe limitations: first, because they require chemical labels and precise optical equipment, they are often inconvenient to use and fragile; and second, they can’t easily be shrunk and integrated into a microchip.
Manalis says his method for the direct detection of biomolecules does not suffer those drawbacks. Because it doesn’t use fluorescence, it doesn’t use an optical reader. That, says Manalis, makes it “much more robust. You can drop it.”
And because its manufacture relies on the same basic process as any other silicon microchip’s, the detector can be easily miniaturized and combined with other silicon components. A series of tiny, nearly identical microchannels could be fabricated alongside each other, yielding a device capable of rapidly measuring many different types of samples.