Nanocantilevers as future disease detectors

Researchers at Purdue University have made a discovery about the behavior of tiny structures called nanocantilevers that could be crucial in designing a new class of ultra-small sensors for detecting viruses, bacteria, and other pathogens.

The nanocantilevers, which resemble tiny diving boards made of silicon, could be used in future disease detectors because they vibrate at different frequencies when molecules stick to them, revealing the presence of substances associated with cancer or other illnesses.

The researchers were surprised to learn that the cantilevers, coated with antibodies to detect certain viruses, attract different densities – or quantity of antibodies per area – depending on the size of the cantilever. The devices are immersed into a liquid containing the antibodies to allow the proteins to stick to the cantilever surface.

"But instead of simply attracting more antibodies because they are longer, the longer cantilevers also contained a greater density of antibodies, which was very unexpected," said Rashid Bashir, Ph.D., who directed this research. The research also shows that the density is greater toward the free end of the cantilevers. This work appears in the Proceedings of the National Academy of Sciences.

The engineers found that the cantilevers vibrate faster after the antibody attachment if the devices have about the same nanometer-range thickness as the protein layer. Moreover, the longer the protein-coated nanocantilever, the faster the vibration, which could only be explained if the density of antibodies were to increase with increasing lengths, Bashir said. The research group confirmed this hypothesis using optical measurements and then developed a mathematical model that describes the behavior. The information and resulting model will be essential to properly design future "nanomechanical" sensors that use cantilevers, Bashir said.

The cantilevers studied in the recent work range in length from a few microns to tens of microns, or millionths of a meter, and are about 20 nanometers thick, which is also roughly the thickness of the antibody coating. A cantilever naturally "resonates," or vibrates at a specific frequency, depending on its mass and mechanical properties. The mass changes when contaminants land on the devices, causing them to vibrate at a different "resonant frequency," which can be quickly detected. Because certain proteins attract only specific contaminants, the change in vibration frequency means a particular contaminant is present.

Ordinarily, when using cantilevers that are on a thickness scale of microns or larger, attaching mass causes the resonant frequency to decrease, which is the opposite of what occurs with the nanoscale-thickness cantilevers. Researchers believe the unexpected behavior is a result of the antibodies being about the same thickness as the ultra-thin nanocantilevers, meaning their vibration is more profoundly affected than a more massive cantilever would be by the attachment of the antibodies.

"The conclusion is that when the attached mass is as thick as the cantilever, then you not only affect the mass but you also affect a key property called the net stiffness constant and the resonant frequency can actually go up," Bashir said.

This work is detailed in a paper titled, "Anomalous resonance in a nanomechanical biosensor." An abstract of this paper is available through PubMed. View abstract.