Single-protein nanomechanical mass spectrometry in real time

Hanay, M. Selim; Kelber, Scott; Naik, Akshay; Chi, Derrick; Hentz, Sébastien; Bullard, Elizabeth Caryn; Colinet, Éric; Duraffourg, Laurent; Roukes, M. L.

doi:10.1038/nnano.2012.119

Cited by 472 publications

(526 citation statements)

References 39 publications

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“…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. We envision that the mass, position and orientation-dependent stiffness can be obtained by tracking the frequency of multiple vibration modes and solving the inverse problem 8,[10][11] . In addition, the implementation of imaging techniques that can approximately resolve the position of the adsorbate on the cantilever can simplify the problem and reduce the error in the calculations [31][32] .…”

Section: Discussionmentioning

confidence: 99%

“…The use of ultrathin cantilevers with thickness below 100 nm is justified to boost the stiffness effect. The proposed technology is feasible as ultrathin cantilevers can routinely be fabricated and methods for the delivery of biological particles one by one to the resonator in vacuum have been demonstrated [9][10] . 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.…”

mentioning

confidence: 99%

“…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][9][10][11] and its stiffness 1 . The use of ultrathin cantilevers with thickness below 100 nm is justified to boost the stiffness effect.…”

mentioning

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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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

mentioning

confidence: 99%

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Physics of Nanomechanical Spectrometry of Viruses

Ruz¹,

Tamayo²,

Pini³

et al. 2014

Sci Rep

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“…Two applications with particular promise are force microscopy in geometries that transcend the constraints of conventional atomic force microscopy (AFM) [1][2][3] and on-chip mass spectrometry with single molecule sensitivity. [4][5][6] Another burgeoning nanotechnology is quantum nanosensors based upon the electron spin of the NV center in diamond. The NV center has been used to locate single elementary charges, 7 to perform thermometry within living cells 8 and to realize nanoscale MRI in ambient conditions.…”

Section: Textmentioning

confidence: 99%

Nanomechanical Sensing Using Spins in Diamond

et al. 2017

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KEYWORDSNitrogen-vacancy center, diamond, spin-mechanical interaction, nanomechancial sensing, NEMS 2 ABSTRACT Nanomechanical sensors and quantum nanosensors are two rapidly developing technologies that have diverse interdisciplinary applications in biological and chemical analysis and microscopy.For example, nanomechanical sensors based upon nanoelectromechanical systems (NEMS) have demonstrated chip-scale mass spectrometry capable of detecting single macromolecules, such as proteins. Quantum nanosensors based upon electron spins of negatively-charged nitrogen-vacancy (NV) centers in diamond have demonstrated diverse modes of nanometrology, including single molecule magnetic resonance spectroscopy. Here, we report the first step towards combining these two complementary technologies in the form of diamond nanomechanical structures containing NV centers. We establish the principles for nanomechanical sensing using such nano-spinmechanical sensors (NSMS) and assess their potential for mass spectrometry and force microscopy. We predict that NSMS are able to provide unprecedented AC force images of cellular biomechanics and to, not only detect the mass of a single macromolecule, but also image its distribution. When combined with the other nanometrology modes of the NV center, NSMS potentially offer unparalleled analytical power at the nanoscale. TEXTNanomechanical sensors based upon nanoelectromechanical systems (NEMS) are a burgeoning nanotechnology with diverse microscopy and analytical applications in biology and chemistry. Two applications with particular promise are force microscopy in geometries that transcend the constraints of conventional atomic force microscopy (AFM) 1-3 and on-chip mass spectrometry with single molecule sensitivity. [4][5][6] Another burgeoning nanotechnology is quantum nanosensors based upon the electron spin of the NV center in diamond. The NV center has been 3 used to locate single elementary charges, 7 to perform thermometry within living cells 8 and to realize nanoscale MRI in ambient conditions. 9-11 However, there is yet to be a nanosensing application of the NV center that exploits its susceptibility to local mechanical stress/ strain.Here, we propose that the mechanical susceptibility of the NV center's electron spin can be exploited together with the extreme mechanical properties of diamond nanomechanical structures to realize nano-spin-mechanical sensors (NSMS) that outperform the best available technology. Such NSMS will be capable of both high-sensitivity nanomechanical sensing and the quantum nanosensing of electric fields, magnetic fields and temperature. NSMS will thereby constitute the unification of two burgeoning nanotechnologies and have the potential to perform such unparalleled analytical feats as mass-spectrometry and MRI of single molecules. As the first step towards realizing NSMS, we report the complete characterization of the spin-mechanical interaction of the NV center. We use this to establish the design and operating principles of diamond NSMS and to perfor...

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“…1,2 Different types of microstructures, such as cantilever and clamped-clamped microbeams, have been employed for resonance sensing. [3][4][5][6] Classically, the shift of the natural frequency of a microstructure is tracked to determine the amount of adsorbed mass attached on the functionalized surface. As the demand for smarter sensors grows larger, new techniques for mass detection have emerged.…”

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confidence: 99%

A smart microelectromechanical sensor and switch triggered by gas

Bouchaala

Jaber

Shekhah

et al. 2016

Applied Physics Letters

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There is an increasing interest to realize smarter sensors and actuators that can deliver a multitude of sophisticated functionalities while being compact in size and of low cost. We report here combining both sensing and actuation on the same device based on a single microstructure. Specifically, we demonstrate a smart resonant gas (mass) sensor, which in addition to being capable of quantifying the amount of absorbed gas, can be autonomously triggered as an electrical switch upon exceeding a preset threshold of absorbed gas. Toward this, an electrostatically actuated polymer microbeam is fabricated and is then functionalized with a metal-organic framework, namely, HKUST-1. The microbeam is demonstrated to absorb vapors up to a certain threshold, after which is shown to collapse through the dynamic pull-in instability. Upon pull-in, the microstructure can be made to act as an electrical switch to achieve desirable actions, such as alarming.

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Single-protein nanomechanical mass spectrometry in real time

Cited by 472 publications

References 39 publications

Physics of Nanomechanical Spectrometry of Viruses

Physics of Nanomechanical Spectrometry of Viruses

Nanomechanical Sensing Using Spins in Diamond

A smart microelectromechanical sensor and switch triggered by gas

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