Nanomechanical resonator arrays: a springboard to single-molecule detection
Nanomechanical resonators are flexible nanoscale structures resembling tiny diving boards or harmonica reeds. Like all cantilevers (beams anchored at only one end), they vibrate most strongly at specific resonant frequencies. The small size of a nanomechanical resonator means that the adherence of any foreign matter to its surface can potentially alter its resonant frequency. Monitoring this frequency shift permits biological and chemical agents to be detected with single-molecule resolution, providing better sensitivity than that found in commercially available mass spectrometers.
In order to make nanomechanical resonators practical for real-world sensing applications, the dual requirements of high sensitivity and rapid detection must be met. The low probability that a target molecule will land on the device’s small sensing area limits robustness and performance, and in the past researchers have resorted to the impractical solution of aiming a high-volume chemical stream directly at an individual resonator. 
An alternate approach is to construct a large array of resonators, thus eliminating the need for pinpoint physical targeting. An early demonstration of this concept was provided by the Millipede project at IBM Zurich (although the thousands of microcantilevers in that array were designed not to sense molecules but to implement a data storage system).
The high sensitivity and small size of nanomechanical resonators enables large-scale integration and device miniaturization and promises a new generation of portable biological and chemical sensors. Potential applications of nanomechanical resonator array-based sensors include breath analyzers, industrial and food processing, national security and defense, and food and water quality monitoring. 
Nanomechanical resonator sensors have proven to be particularly successful in biological and medical applications, with reports of their use in the detection of biomolecules such as DNA and RNA, bacteria such as Escherichia coli and Salmonella enterica, and even tumor cells. One example used resonators coated with a nutrient layer in which the growth of E. coli was revealed by continuous changes in the resonant frequency. 
In another study, virus researchers at Purdue University found that coating resonators with antibodies changed the frequency in unexpected ways. The effect turned out to be due to a complex influence of resonator area on coating density. 
Who, Where, and When?
In 2003, Ming Su, Shuyou Li, and Vinayak P. Dravid at the Department of Materials Sciences and Engineering and Institute for Nanotechnology, Northwestern University, described the use of multiple resonators to detect multiple DNA sequences simultaneously.
Now researchers at the Alliance for Nanosystems VLSI, a joint venture of Caltech’s Kavli Nanoscience Institute and CEA-LETI’s MINATEC, Grenoble, have created arrays consisting of thousands of individual nanoresonators at densities of up to six million resonators per square centimeter. When coated with a polymer having a high affinity for the chemical warfare agent diisopropyl methylphosphonate, the device successfully detected 1 ppb of the gas within two seconds. Nanosensor arrays of this sort could form the basis of a gas chromatograph/mass spectrometer on a chip.
In general, nanomechanical resonators are fabricated either by etching three-dimensional structures into a silicon wafer or by building up layers on the surface of a polymer-based carrier substrate (surface micromachining). Other technologies include ZnO or rhodium nanowires, carbon nanotubes, and graphene.
The massive arrays produced by the Kavli-MINATEC team were created using standard lithographic methods for mass-producing computer chips. Complex electrical couplings between the resonators ensured good sensor performance even if lithographic defects, mechanical damage, or electrostatic discharge caused individual resonators to fail.
To achieve the accurate and fast readout required, various technologies exist, including: optical (laser beam deflection, as in the Penn State experiment); capacitive (capacitance change between the resonator and a parallel plate); piezoelectrical (change in electrical potential due to mechanical stress); and piezoresistive (change in resistance due to mechanical stress, as in the Kavli-MINATEC nanoresonator array).
It may be possible to push the limits of measurement beyond single-molecule sensing. Due to their small scale, nanomechanical resonators exhibit quantum mechanical behavior when laser-cooled to their quantum ground state. In certain regimes, therefore (at near-zero temperatures and sufficiently high resonance frequencies), large arrays of these devices could in principle be used to achieve even higher-resolution measurements.
Some fundamental mechanisms of cantilever sensors are not yet completely understood. For example, at this mesoscopic scale, random collisions with gas molecules can result in significant thermomechanical noise. While the input of multiple sensors may assist in noise detection and suppression, much work remains to be done in characterizing and tracing the origin of surface stress changes.
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