Diagnosis and monitoring of complex diseases such as cancer require quantitative detection of multiple proteins. Recent work has shown that when specific biomolecular binding occurs on one surface of a microcantilever beam, intermolecular nanomechanics bend the cantilever, which can be optically detected. Although this label-free technique readily lends itself to formation of microcantilever arrays, what has remained unclear is the technologically critical issue of whether it is sufficiently specific and sensitive to detect disease-related proteins at clinically relevant conditions and concentrations. As an example, we report here that microcantilevers of different geometries have been used to detect two forms of prostate-specific antigen (PSA) over a wide range of concentrations from 0.2 ng/ml to 60 microg/ml in a background of human serum albumin (HSA) and human plasminogen (HP) at 1 mg/ml, making this a clinically relevant diagnostic technique for prostate cancer. Because cantilever motion originates from the free-energy change induced by specific biomolecular binding, this technique may offer a common platform for high-throughput label-free analysis of protein-protein binding, DNA hybridization, and DNA-protein interactions, as well as drug discovery.

It is well known that bimetallic microcantilevers can exhibit static deflection as a result of thermal effects, including exothermic adsorption of chemicals on their surfaces. It is shown here that the resonance frequency of a cantilever can change due to a combination of mass loading and change of spring constant resulting from adsorption of chemicals on the surface. Cantilevers also undergo static bending that is induced by differential surface stress. The magnitude of these effects depends upon the chemical properties of the surface and upon the amount of material adsorbed. Hence cantilever deflection as well as resonance frequency change can be used as the basis for development of novel chemical sensors.

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Generation of nanomechanical cantilever motion from biomolecular interactions can have wide applications, ranging from highthroughput biomolecular detection to bioactuation. Although it has been suggested that such motion is caused by changes in surface stress of a cantilever beam, the origin of the surface-stress change has so far not been elucidated. By using DNA hybridization experiments, we show that the origin of motion lies in the interplay between changes in configurational entropy and intermolecular energetics induced by specific biomolecular interactions. By controlling entropy change during DNA hybridization, the direction of cantilever motion can be manipulated. These thermodynamic principles were also used to explain the origin of motion generated from protein-ligand binding. U nderstanding the mechanisms of how biological reactions produce motion is fundamental to several physiological processes (1-3). Although most past effort (4-6) has focused on studying single molecular motors (7-9), recent experiments (10, 11) by using microcantilever beams have led to observations that multiple DNA hybridization and antigen-antibody reactions can collectively produce nanomechanical motion. The promising prospects of interfacing molecular biology with micro-and nanomechanical systems can best be exploited if we learn how to control and manipulate nanomechanical motion generated by biomolecular interactions. Although an understanding of the origins of this motion would allow such control, it has so far remained elusive. It has been suggested (11) that the motion is induced by changes in surface stress of the cantilever caused by biomolecular binding. Although this may be true, the origin of surface-stress change is not understood. In this paper, we show that cantilever motion is created because of the interplay between changes in configurational entropy and intermolecular energetics induced by specific biomolecular reactions. The entropy contribution can be critical in determining the direction of motion. By using thermodynamic principles in conjunction with DNA hybridization experiments, we demonstrate that both the direction and magnitude of cantilever motion can be controlled. These thermodynamic principles are also used to explain the nanomechanical motion created by protein-ligand binding. Materials and MethodsExperimental Setup and Approach. Fig. 1 illustrates the experiment we used for studying nanomechanical motion created by multiple specific biomolecular reactions. The experimental setup consisted of a transparent fluid cell, within which a gold-coated silicon nitride (Au͞SiN x ) cantilever was mounted. The fluid cell and the V-shaped micromechanical silicon nitride cantilevers were purchased from Digital Instruments (Santa Barbara, CA). The cantilevers used were 200 m long and 0.5 m thick, and each leg was 20 m wide. The gold films originally coated on cantilevers were etched away, and a fresh 25-nm-thick gold coating was deposited. For good adhesion between gold and silicon nitride, a 5-nm-thick chro...

Oscillating silicon nitride microcantilevers coated with a thin gold film have been used to detect mercury vapor in air. Cantilever resonance frequency changes due to surface mass loading as a result of adsorption of mercury vapor. Furthermore, cantilever bending is also altered due to changes in surface stress induced by mercury adsorption on the gold overlayer. Both of these phenomena can be used to quantitatively detect adsorbed vapors with picogram mass resolution.

The direct conversion of mechanical energy into electricity by nanomaterial-based devices offers potential for green energy harvesting . A conventional triboelectric nanogenerator converts frictional energy into electricity by producing alternating current (a.c.) triboelectricity. However, this approach is limited by low current density and the need for rectification . Here, we show that continuous direct-current (d.c.) with a maximum density of 10 A m can be directly generated by a sliding Schottky nanocontact without the application of an external voltage. We demonstrate this by sliding a conductive-atomic force microscope tip on a thin film of molybdenum disulfide (MoS). Finite element simulation reveals that the anomalously high current density can be attributed to the non-equilibrium carrier transport phenomenon enhanced by the strong local electrical field (10-10 V m) at the conductive nanoscale tip . We hypothesize that the charge transport may be induced by electronic excitation under friction, and the nanoscale current-voltage spectra analysis indicates that the rectifying Schottky barrier at the tip-sample interface plays a critical role in efficient d.c. energy harvesting. This concept is scalable when combined with microfabricated or contact surface modified electrodes, which makes it promising for efficient d.c. triboelectricity generation.

The deflection of scanning force microscope cantilevers, metal coated on one side, is significantly influenced by both thermal heating and variations in relative humidity. For constant relative humidity, the deflection of the cantilever drifts due to laser heating and eventually reaches a steady-state value. For a thermally stabilized cantilever, the deflection varies linearly with relative humidity. Exposure to other vapors, such as mercury, changes the inherent deflection of the cantilever. Relative amounts of adsorbates on the cantilever can be estimated from shifts in the cantilever resonance frequency with picogram mass resolution. The cantilever deflection as well as changes in resonance frequency due to vapor adsorption can be used as basis for novel chemical sensors.

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