Portland, Ore. - Detection of a single virus particle was recently demonstrated for the first time in a sensor based on microelectromechanical systems (MEMS). The tiny cantilever, measuring just 1 x 4 microns x 20 nanometers thick, vibrates at a fixed frequency until a virus particle lands on it, which changes its resonance enough to be detected. A single particle of vaccinia-a virus that forms the basis for the smallpox vaccine-weighs only 9 femtograms, or quadrillionths of a gram.
"Our first task was to show that it was possible to build a cantilever small and sensitive enough that the added mass of even a single virus particle could be detected by changing the cantilever's resonant frequency," said Rashid Bashir, an associate professor of electrical, computer and biomedical engineering working at the Birck Nanotechnology Center at Purdue University (West Lafayette, Ind.).
Bashir's research group, including senior research scientist Demir Akin and doctoral student Amit Gupta, plan next to functionalize the cantilever so that only specific virus particles stick to it. Then they will characterize methods of concentrating air samples in a microfluidic device for detection of airborne virus particles.
"As the basis for future microfluidic-based chemistry labs-on-a-chip, the tiny cantilevers could be fabricated by the thousands in side-by-side arrays capable of simultaneously detecting many different toxins, pathogens and bioagents," said Bashir.
Applications for homeland security could be supplemented with consumer applications in environmental and health monitoring, Bashir said.
Currently, biosensing systems designed to detect a virus require that the DNA inside the virus first be extracted; it is the DNA that is then detected. But this cannot be done with single particles in real-time, and moreover the technique requires that a virus be destroyed to get at its DNA. Bashir's method, however, keeps a virus intact for further analysis after detection.
To create a real-time detector, Bashir turned to measuring the virus' mass with a cantilever rather than using chemicals to analyze its DNA. The cantilever was etched out of silicon using semiconductor fabrication techniques. Silicon deposited atop a wafer was formed into patterns with lithography; chemical etching then removed the layers around the cantilever, leaving it freestanding except for a connection at its base.
Cantilevers are diving-board-shaped structures that vibrate at a frequency determined by their shape. Bashir's test cantilevers range from 4 to 5 microns in length, 1 to 2 micron in width and 20 to 30 nm thick. Since the structures are so small and lightweight, their resonant frequency can be altered by their mass. Bashir's task was to design a cantilever small and light enough for a single virus particle (9 femtograms) to alter its frequency.
"We had to design them so that a single virus particle's weight would make a big enough difference, but we also had to make sure the resonant frequency was low enough to be easily measured," he said.
Due to the thermal and ambient noise associated with the tiny MEMS device, Bashir's team measured its resonant frequency using a laser Doppler vibrometer, thereby completing phase one of their work. In phase two and three, respectively, Bashir will experiment with coatings for the cantilever that bind only to a specific virus.
Bashir's work was funded by the National Institutes of Health and the Birck Nanotechnology Center.