The properties of water at the nanoscale are crucial in many areas of biology, but the confinement of water molecules in sub-nanometre channels in biological systems has received relatively little attention. Advances in nanotechnology make it possible to explore the role played by water molecules in living systems, potentially leading to the development of ultrasensitive biosensors. Here we show that the adsorption of water by a self-assembled monolayer of single-stranded DNA on a silicon microcantilever can be detected by measuring how the tension in the monolayer changes as a result of hydration. Our approach relies on the microcantilever bending by an amount that depends on the tension in the monolayer. In particular, we find that the tension changes dramatically when the monolayer interacts with either complementary or single mismatched single-stranded DNA targets. Our results suggest that the tension is mainly governed by hydration forces in the channels between the DNA molecules and could lead to the development of a label-free DNA biosensor that can detect single mutations. The technique provides sensitivity in the femtomolar range that is at least two orders of magnitude better than that obtained previously with label-free nanomechanical biosensors and with label-dependent microarrays.
The authors present a theoretical model to predict the resonance frequency shift due to molecule adsorption on micro-and nanocantilevers. They calculate the frequency shift experienced by cantilevers made of either silicon or the polymer SU-8, when two adsorbates, myosin protein and an alkanethiol, are attached to the cantilever surface. They demonstrate that the effect of the adsorbate stiffness can be comparable or even larger than the mass effect, producing positive frequency shifts. The results provide methods for decoupling both opposite effects and routes for the design of resonators with high sensitivity to molecule adsorption based on either stiffness or mass effects. © 2006 American Institute of Physics. ͓DOI: 10.1063/1.2388925͔ Microcantilever resonators have been proposed for highly sensitive label-free detection of organic and biological molecules. [1][2][3] The basic principle is the measurement of the resonance frequency shift due to the added mass of the molecules bound to the cantilever surface. The sensitivity is inversely proportional to the active mass of the resonator. Advances in micro-and nanofabrication techniques have motivated an intense effort for scaling the resonator size down in order to push the detection limits. 2,3 Thus the sensitivity of the technique has rapidly evolved from the picogram to the attogram range, by simply reducing the size of the resonators ͑lengthϫ widthϫ thickness͒ from ͑100-500͒ ϫ ͑20-100͒ ϫ ͑0.5-1͒ to ͑5-20͒ ϫ ͑0.5-2͒ ϫ ͑0.1-0.3͒ m 3 . Consequently, the resonance frequency increases from the kilohertz to the megahertz regime. By further reduction of the size to the nanoscale, the detection limits can achieve unprecedented values. 3 Independently of the cantilever size, the quantification of the adsorbed mass is an issue still not resolved. First, when the molecules are not uniformly adsorbed, the resonance frequency critically depends on the distribution of the molecules on the resonator. 4,5 Second, a discrepancy is, in many cases, found between the added mass calculated by the theory and the mass adsorbed on the cantilever. This discrepancy is generally justified by invoking the effect of the adsorption-induced surface stress on the resonance frequency. 6 In this effect, the surface stress is simplified to an external axial force that creates a shearing moment. Recently, Lu et al. 7 have demonstrated that this model is inadequate to describe the physical system because in the real situation, the cantilever free end allows the deformation to relieve the stress. In their theoretical treatment, a strain-dependent surface stress is necessary to observe some effect on the resonant frequency, and therefore the surface stress effect is expected to be negligible in biomolecular applications.Up to date, the influence of the mechanical properties of the adsorbed molecules on the resonance has been neglected. In this work, we present a theoretical model to study the effect of the stiffness of the molecules bound to a microcantilever on the resonance frequency. We demo...
By performing experiments of adsorption of the bacteria Escherichia coli on singly clamped microcantilevers, we demonstrate that the effect of the added mass is not the only and may not be the main origin of the response of these sensors. The experiments show that the magnitude and sign of resonance frequency shift both depend critically on the distribution of the adsorbed bacterial cells on the cantilever. We relate this behavior to the added mass that shifts the resonance to lower frequencies and the higher effective flexural rigidity of the cantilever due to the bacteria stiffness that shifts the resonance to higher frequencies. Both effects can be uncoupled by positioning the cells where each effect dominates, near the free cantilever end for measuring the added mass or near the clamping for measuring the increase of flexural rigidity.We propose a model that accounts for the mechanical properties of the attached bacteria that increase the stiffness of the cantilever. We model our cantilever as an Euler-Bernoulli beam, in which both the mass per unit length and the flexural rigidity are dependent on the longitudinal positionTo calculate the resonance frequency we have applied Rayleigh's approximation. This method deduces the resonance frequencies by performing an energy-work balance and assuming that the eigenmode shapes are not substantially changed by the adsorbed bacteria resonance frequency is calculated as
We report the selective excitation of the flexural modes of microcantilevers in aqueous solutions, by applying the photothermal excitation technique. The experiments show that a particular vibration mode can be efficiently excited by focusing the intensity-modulated laser beam on regions of high curvature of the vibration shape. In addition, the resulting resonant peaks in liquid appear distorted by an amplitude component that decreases with the frequency. This distortion produces a shift of the resonance to lower frequencies. A theoretical model based on the transformation of optical energy into mechanical energy via an intermediate thermal stage is proposed to interpret the experimental results. The theory shows that the driven oscillation of the cantilever depends on the curvature of the eigenmode at the excitation position and the heating induced by the excitation laser, which decreases with the frequency. The results reported here set the basis for efficient excitation of high vibration modes in liquids and for optimized design of optically driven microresonators.
We have measured the effect of the bacteria adsorption on the resonant frequency of microcantilevers as a function of the adsorption position and vibration mode. The resonant frequencies were measured from the Brownian fluctuations of the cantilever tip. We found that the sign and amount of the resonant frequency change is determined by the position and extent of the adsorption on the cantilever with regard to the shape of the vibration mode. To explain these results, a theoretical one-dimensional model is proposed. We obtain analytical expressions for the resonant frequency that accurately fits the data obtained by the finite element method. More importantly, the theory data
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