Effect of the adsorbate stiffness on the resonance response of microcantilever sensors

Tamayo, Javier; Ramos, Daniel; Mertens, Johan; Calleja, Montserrat

doi:10.1063/1.2388925

Cited by 157 publications

(159 citation statements)

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“…This is necessary to obtain i) a correct quantification of the amount of target in the sample and ii) for obtaining those parameters that allow optimization of the sensor response. Recently, we have found that in addition to the added mass, nanomechanical resonators are very sensitive to the stiffness of the adsorbed molecules [12,13]. The problem is that both effects produce opposite shifts of the resonant frequency being detrimental to the sensitivity.…”

Section: Introductionmentioning

confidence: 99%

Detection of bacteria based on the thermomechanical noise of a nanomechanical resonator: origin of the response and detection limits

et al. 2007

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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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Section: Introductionmentioning

confidence: 99%

Detection of bacteria based on the thermomechanical noise of a nanomechanical resonator: origin of the response and detection limits

et al. 2007

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“…A key piece in this approach is a model that accounts for the effect of the stiffness of the biological particles on the recorded jumps in the resonant frequencies. So far, the only model that accounts for this effect assumes that the adsorbate length is much larger than its thickness and hence the adsorbate can effectively be approximated by a thin layer on a cantilever region 12 . The case of single biological entities, such as proteins and viruses, is significantly more challenging.…”

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confidence: 99%

“…The resonance frequency of the cantilever can be quantified by equaling the mean potential and kinetic energies per oscillation cycle, referred to as Rayleigh-Ritz method 12 ,…”

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confidence: 99%

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Physics of Nanomechanical Spectrometry of Viruses

Ruz¹,

Tamayo²,

Pini³

et al. 2014

Sci Rep

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There is an emerging need of nanotools able to quantify the mechanical properties of single biological entities. A promising approach is the measurement of the shifts of the resonant frequencies of ultrathin cantilevers induced by the adsorption of the studied biological systems. Here, we present a detailed theoretical analysis to calculate the resonance frequency shift induced by the mechanical stiffness of viral nanotubes. The model accounts for the high surface-to-volume ratio featured by single biological entities, the shape anisotropy and the interfacial adhesion. The model is applied to the case in which tobacco mosaic virus is randomly delivered to a silicon nitride cantilever. The theoretical framework opens the door to a novel paradigm for biological spectrometry as well as for measuring the Young's modulus of biological systems with minimal strains.I t is increasingly evident the intimate link between the mechanical properties of biological systems and its role in fundamental biological processes and disease 1 . This link spans from the molecular scale to the tissue scale. For example, the elasticity of cells has become a reliable indicator of cell transformation into cancerous or metastatic cells [2][3] . Similarly, recent reports have demonstrated the biological relevance of the mechanical properties of viruses. Viruses are able to dynamically modulate their mechanical properties in response to external forces, so as to withstand those forces or to ease cell infection 4 . For instance, in the human immunodeficiency and murine leukemia viruses, the stiffness largely decreases during the maturation process, acting as a mechanical switch for the infection process 5 . Strikingly, a single point mutation in the capsid protein of some viruses can significantly change their elasticity 6 . It is therefore fundamental the development of nanotools that enable the accurate quantification of the nanomechanical properties of single biological entities with high throughput. These tools can provide new insights on how the structural conformation, biological function, and mechanical properties of biomolecules and their hierarchical assemblies are related each other. The most prominent method to measure the mechanical properties of biological entities has been so far nanoindentation with the cantilever/tip assembly of an atomic force microscope (AFM) 7 . However, a number of challenges exist with the AFM for the quantification of the mechanical properties. Mainly, the nanoindentation curves strongly depend on the nanometer-scale geometry of the tip/sample contact, which in most of the cases cannot be controlled. Other difficulties include the contribution of the underlying substrate, the effect of adhesion, non-linear loading and the lack of accurate theoretical models.We envisage a novel biological spectrometry technique based on the measurement of several vibration modes of ultrathin micro-and nanocantilevers for the identification of adsorbed biomolecules and biological systems by two coordinates: the mass 8-11 an...

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“…1A), which is fundamentally unachievable by exclusive use of existing nanoscale electrical or mechanical biosensors. Moreover, the reliance of change in stiffness (23,24) ensures screening-free detection of charged/neutral molecules, with no need for a reference electrode, and the measurement of drain current for detection requires no complex instrumentation. It should be noted that from a mechanical perspective, the Flexure-FET operates close to pull-in instability, a critical point.…”

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confidence: 99%

Flexure-FET biosensor to break the fundamental sensitivity limits of nanobiosensors using nonlinear electromechanical coupling

Jain

Nair

Alam

2012

Proc. Natl. Acad. Sci. U.S.A.

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In this article, we propose a Flexure-FET (flexure sensitive field effect transistor) ultrasensitive biosensor that utilizes the nonlinear electromechanical coupling to overcome the fundamental sensitivity limits of classical electrical or mechanical nanoscale biosensors. The stiffness of the suspended gate of Flexure-FET changes with the capture of the target biomolecules, and the corresponding change in the gate shape or deflection is reflected in the drain current of FET. The Flexure-FET is configured to operate such that the gate is biased near pull-in instability, and the FET-channel is biased in the subthreshold regime. In this coupled nonlinear operating mode, the sensitivity (S) of Flexure-FET with respect to the captured molecule density (N s ) is shown to be exponentially higher than that of any other electrical or mechanical biosensor.In other words, while S Flexure ∼ e ðγ 1 ffiffiffiffi N s p −γ 2 N s Þ , classical electrical or mechanical biosensors are limited to S classical ∼ γ 3 N S or γ 4 lnðN S Þ, where γ i are sensor-specific constants. In addition, the proposed sensor can detect both charged and charge-neutral biomolecules, without requiring a reference electrode or any sophisticated instrumentation, making it a potential candidate for various low-cost, point-of-care applications.label-free detection | genome sequencing | cantilever | spring-softening | critical-point sensors N anoscale biosensors are widely regarded as a potential candidate for ultrasensitive, label-free detection of biochemical molecules. Among the various technologies, significant research have focused on developing ultrasensitive nanoscale electrical (1) and mechanical (2) biosensors. Despite remarkable progress over the last decade, these technologies have fundamental challenges that limit opportunities for further improvement in their sensitivity ( Fig. 1A) (3-6). For example, the sensitivity of electrical nanobiosensors such as Si-Nanowire (NW) FET (field effect transistor) (Fig. 1B) is severely suppressed by the electrostatic screening due to the presence of other ions/charged biomolecules in the solution (7), which limits its sensitivity to vary linearly (in subthreshold regime) (3, 7) or logarithmically (in accumulation regime) (4,7,8,9) with respect to the captured molecule density N s . Moreover, the miniaturization and stability of the reference electrode have been a persistent problem, especially for lab-onchip applications (1). Finally, it is difficult to detect charge-neutral biological entities such as viruses or proteins using chargebased electrical nanobiosensor schemes.In contrast, nanomechanical biosensors like nanocantilevers (10, 11) (Fig. 1C) do not require biomolecules to be charged for detection. Here, the capture of target molecules on the cantilever surface modulates its mass, stiffness, and/or surface stress (5,11,12). This change in the mechanical properties of the cantilever can then be observed as a change in its resonance frequency (dynamic mode), mechanical deflection, or change in the resist...

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Effect of the adsorbate stiffness on the resonance response of microcantilever sensors

Cited by 157 publications

References 13 publications

Detection of bacteria based on the thermomechanical noise of a nanomechanical resonator: origin of the response and detection limits

Detection of bacteria based on the thermomechanical noise of a nanomechanical resonator: origin of the response and detection limits

Physics of Nanomechanical Spectrometry of Viruses

Flexure-FET biosensor to break the fundamental sensitivity limits of nanobiosensors using nonlinear electromechanical coupling

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