Prion Protein Detection Using Nanomechanical Resonator Arrays and Secondary Mass Labeling

Varshney, Madhukar; Waggoner, Philip S.; Tan, Christine; Aubin, Keith L.; Montagna, Richard A.; Craighead, Harold G.

doi:10.1021/ac702153p

Cited by 69 publications

(58 citation statements)

References 38 publications

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“…Craighead and coworkers [169][170][171] have provided the label-free detection of specific marker proteins using resonant MEMS devices. Their detection scheme is based on mass sensing such that the frequency shift arises only from the mass of chemically adsorbed protein molecules.…”

Section: Protein Detectionmentioning

confidence: 99%

“…Their detection scheme is based on mass sensing such that the frequency shift arises only from the mass of chemically adsorbed protein molecules. In their studies, the label-free detection of marker proteins such as prostate specific antigen (PSA) [170] and prion protein [169,171] has been reported. They have also suggested a scheme to improve the detection sensitivity such that the frequency shift due to added mass is amplified using nanoparticles and/or secondary antibodies [169].…”

Section: Protein Detectionmentioning

confidence: 99%

“…Most experimental studies of protein detection using resonators have been performed in either ambient conditions [62,[164][165][166], vacuum conditions [170], or cryogenic, high-vacuum conditions [10,169,171]. Until now, with few exceptions [22,23,172], there have been very few studies on in situ detection of proteins in aqueous environments.…”

Section: Protein Detectionmentioning

confidence: 99%

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Nanomechanical resonators and their applications in biological/chemical detection: Nanomechanics principles

et al. 2011

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Recent advances in nanotechnology have led to the development of nano-electro-mechanical systems (NEMS) such as nanomechanical resonators, which have recently received significant attention from the scientific community. This has not only been for their capability for the label-free detection of bio/chemical-molecules at single-molecule (or atomic) resolution for future applications such as the early diagnostics of diseases such as cancer, but also for their unprecedented ability to detect physical quantities such as molecular weight, elastic stiffness, surface stress, and surface elastic stiffness for adsorbed molecules on the surface. Most experimental works on resonator-based molecular detection have been based on the principle that molecular adsorption onto a resonator surface increases the effective mass, and consequently decreases the resonant frequencies of the nanomechanical resonator. However, this principle is insufficient to provide fundamental insights into resonator-based molecular detection at the nanoscale; this is due to recently proposed novel nanoscale detection principles including various effects such as surface effects, nonlinear oscillations, coupled resonance, and stiffness effects. Furthermore, these effects have only recently been incorporated into existing physical models for resonators, and therefore the universal physical principles governing nanoresonator-based detection have not been completely described. Therefore, our objective in this review is to overview the current attempts to understand the underlying mechanisms in nanoresonator-based detection using physical models coupled to computational simulations and/or experiments. Specifically, we will focus on issues of special relevance to the dynamic behavior of nanoresonators and their applications in biological/chemical detection: the resonance behavior of micro/nano-resonators; resonator-based chemical/biological detection; physical models of various nanoresonators such as nanowires, carbon nanotubes, and graphene. We pay particular attention to experimental and computational approaches that have been useful in elucidating the mechanisms underlying the dynamic behavior of resonators across multiple and disparate spatial/length scales, and the resulting insight into resonator-based detection that has been obtained. We additionally provide extensive discussion regarding potentially fruitful future research directions coupling experiments and simulations in order to develop a fundamental understanding of the basic physical principles that govern NEMS and NEMS-based sensing and detection applications.

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Section: Protein Detectionmentioning

confidence: 99%

Section: Protein Detectionmentioning

confidence: 99%

Section: Protein Detectionmentioning

confidence: 99%

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Nanomechanical resonators and their applications in biological/chemical detection: Nanomechanics principles

et al. 2011

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“…[1][2][3][4][5] The principle is that molecular adsorption on the surface of the resonator gives rise to an increase in the active mass of the resonator that makes the resonance frequency to decrease. The continuous advancements in top-down microand nanofabrication techniques has made possible increasingly smaller nanomechanical resonators with detection limits in the zeptogram range ͑10 −21 g͒.…”

mentioning

confidence: 99%

Exponential tuning of the coupling constant of coupled microcantilevers by modifying their separation

Gil-Santos¹,

Ramos²,

Pini³

et al. 2011

Applied Physics Letters

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Vibration localization in coupled nanomechanical resonators has emerged as a promising concept for ultrasensitive mass sensing. It possesses intrinsic common mode rejection and the mass sensitivity can be enhanced with no need of extreme miniaturization of the devices. In this work, we have experimentally studied the role of the separation between cantilevers that are elastically coupled by an overhang. The results show that the coupling constant exponentially decays with the separation. In consistency with the theoretical expectations, the mass sensitivity is inversely proportional to the coupling constant. Finite element simulations show that the coupling constant can be exponentially reduced by increasing the ratio of the cantilever separation to the overhang length. © 2011 American Institute of Physics. ͓doi:10.1063/1.3569588͔ Nanomechanical resonators such as vibrating cantilevers, doubly clamped beams, and trampolines to name a few geometries have been proposed for ultrasensitive mass sensing. [1][2][3][4][5] The principle is that molecular adsorption on the surface of the resonator gives rise to an increase in the active mass of the resonator that makes the resonance frequency to decrease. The continuous advancements in top-down microand nanofabrication techniques has made possible increasingly smaller nanomechanical resonators with detection limits in the zeptogram range ͑10 −21 g͒. 6 Moreover, resonant nanowires and nanotubes fabricated by bottom-up methods are on the verge of single atom resolution ͑1.6610 −24 g͒. 7,8 The main disadvantage in the fabrication of extremely small nanomechanical resonators is that the deviations and imperfections inherent to the fabrication at nanoscale makes difficult to obtain reproducible mechanical properties and responses to molecular adsorption. In addition, very large scale integration of these resonators is still technologically complex.An approach that is no longer depending on the extreme miniaturization of the devices is the use of coupled nanomechanical resonators fabricated by standard silicon technology. 9-14 When the resonators are identical, the vibration of the eigenmodes is delocalized over the array. In a similar way to the Anderson's localization, the addition of the mass on one of the resonators leads to the spatial localization of the eigenmodes. 9,10,12 Since vibration localization is insensitive to uniform adsorption, coupled nanomechanical resonators allows decoupling of unspecific and specific molecular adsorption in differentially sensitized resonators. Theoretically, the sensitivity of these devices could be enhanced by reducing the mechanical coupling constant with no need of miniaturization of the nanomechanical resonators. 12 Here we have fabricated coupled mechanical systems consisting of two silicon nitride microcantilevers elastically coupled by an overhang at their base. The aim is to study the dependence of the mass sensitivity on the coupling constant that in this work is tuned by changing the separation between cantilevers.An optical m...

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“…Mass sensors based on dynamic mode can potentially achieve sub-femtomolar sensitivity (Llic et al, 2005). The ultrahigh mass sensitivity is counterbalanced with a very low selectivity due to the device contamination with non-sought molecules and salt debris (Varshney et al, 2008). Thus, in practice small bio-molecules, such as proteins or oligonucleotides, can be detected at low concentrations.…”

Section: Nano-electromechanical Devices -Nanocantileversmentioning

confidence: 99%

Nanodiagnostics for Tuberculosis

Veigas¹,

Dória²,

Baptista³

2012

Understanding Tuberculosis - Global Experiences and Innovative Approaches to the Diagnosis

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Prion Protein Detection Using Nanomechanical Resonator Arrays and Secondary Mass Labeling

Cited by 69 publications

References 38 publications

Nanomechanical resonators and their applications in biological/chemical detection: Nanomechanics principles

Nanomechanical resonators and their applications in biological/chemical detection: Nanomechanics principles

Exponential tuning of the coupling constant of coupled microcantilevers by modifying their separation

Nanodiagnostics for Tuberculosis

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