Cantilever Sensors: Nanomechanical Tools for Diagnostics

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Ram Datar, Seonghwan Kim, Sangmin Jeon, Peter Hesketh, Scott Manalis, Anja Boisen, and Thomas Thundat Abstract Cantilever sensors have attracted considerable attention over the last decade because of their potential as a highly sensitive sensor platform for high throughput and multiplexed detection of proteins and nucleic acids. A micromachined cantilever platform integrates nanoscale science and microfabrication technology for the label-free detection of biological molecules, allowing miniaturization. Molecular adsorption, when restricted to a single side of a deformable cantilever beam, results in measurable bending of the cantilever. This nanoscale deflection is caused by a variation in the cantilever surface stress due to biomolecular interactions and can be measured by optical or electrical means, thereby reporting on the presence of biomolecules. Biological specificity in detection is typically achieved by immobilizing selective receptors or probe molecules on one side of the cantilever using surface functionalization processes. When target molecules are injected into the fluid bathing the cantilever, the cantilever bends as a function of the number of molecules bound to the probe molecules on its surface. Massproduced, miniature silicon and silicon nitride microcantilever arrays offer a clear path to the development of miniature sensors with unprecedented sensitivity for biodetection applications, such as toxin detection, DNA hybridization, and selective detection of pathogens through immunological techniques. This article discusses applications of cantilever sensors in cancer diagnosis.

Mass Detection Using Variation in Resonance Frequency As described earlier, the resonance frequency, f, of a cantilever varies sensitively as a function of mass loading (∆m), according to: f=

Introduction The detection of multiple target molecules in a small volume of sample has immediate relevance in the early detection of diseases, such as cancer. It is well known that many cancers can be curatively treated if diagnosed early when the tumors are still small and localized. However, the unfortunate reality is that a significant proportion of cancers are diagnosed only after the tumors have spread distally through blood or lymphatic fluid (metastasized) to multiple locations. Since cancer is a complex disease, its diagnosis will require monitoring for alterations in multiple parameters at molecular, cellular, and tissue levels to provide a comprehensive picture of the extent of the

very attractive. Biosensing technologies based on cantilever arrays have the potential of satisfying this need for multitarget detection with high sensitivity and selectivity using very small volumes of sample. Microcantilevers are micromechanical beams that are anchored at one end, such as diving spring boards, that can be readily fabricated on silicon wafers and other materials. Their typical dimensions are approximately 100 microns long, 20 microns wide, and 1 micron thick. The microcantilever sensors are physical sensors that respond to surf