<i>In situ</i> real-time monitoring of biomolecular interactions based on resonating microcantilevers immersed in a viscous fluid

Kwon, Taeyun; Eom, Kilho; Park, Jae Hong; Yoon, Dae Sung; Kim, Tae Song; Lee, Hong Lim

doi:10.1063/1.2741053

Cited by 68 publications

(57 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For instance, when a microcantilever acting as an AFM tip vibrates in an aqueous environment in order to image a biological sample in an aqueous environment [89,90], the hydrodynamic effect significantly deteriorates the resonance behavior of microcantilever, and consequently restricts the resolution of the AFM image. Furthermore, cantilever sensors have recently been employed for in situ detection of biological molecules and/or biomolecular interactions in an aqueous environment [22,23,26,45,91], where the hydrodynamic effect significantly reduces the resonant frequencies, which consequently reduces the detection sensitivity. The hydrodynamic effect also has a significant impact on the resonance behavior of NEMS in air.…”

Section: Resonance Behavior In An Aqueous Environmentmentioning

confidence: 99%

“…(15). However, in the works by Kirstein et al [99], Kwon et al [22], and Dareing et al [100], an added mass and fluid damping terms were heuristically introduced based on the hydrodynamic force given by Eq. (13) in order to predict the resonance behavior of a cantilever with circular cross-sectional shape.…”

Section: Resonance Behavior In An Aqueous Environmentmentioning

confidence: 99%

“…For instance, micro/nano-electro-mechanical system (MEMS/NEMS) devices have allowed the sensitive detection of physical quantities such as spin [4,5], molecular mass [6][7][8][9][10], quantum state [11] (see also Refs. [12][13][14] which discuss the prospect of NEMS for studying quantum mechanics), thermal fluctuation [15][16][17][18], coupled resonance [19][20][21], and biochemical reactions [22][23][24][25][26]. Among MEMS/NEMS devices, nanomechanical resonators have been recently highlighted for their unprecedented dynamic characteristics as they can easily reach ultra-high-frequency (UHF) and/or very-high-frequency (VHF) dynamic behavior up to the Giga Hertz (GHz = 10 9 Hz) regime [3,[27][28][29].…”

Section: Introductionmentioning

confidence: 99%

“…In recent years, micro/nano-mechanical resonators have also received significant attention for their capability of label-free detection of specific biological molecules [10,22,37,38] and/or cells [25,39,40], even at low concentrations, that are relevant to specific diseases such as cancer [41,42]. However, current biosensing tools such as enzyme-linked immunosorbent assay (ELISA) exhibits a key restriction in that they are unable to accurately detect marker proteins (relevant to specific cancers) in the concentration of ~1 ng/ml, which is known as the "diagnostic gray zone" [43], in blood serum.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

et al. 2011

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Resonance Behavior In An Aqueous Environmentmentioning

confidence: 99%

Section: Resonance Behavior In An Aqueous Environmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2011

Self Cite

View full text Add to dashboard Cite

show abstract

“…On the other hand, low affinity or transient interactions, which are more relevant to biological systems, have not been measured in a high-throughput format. More recent alternatives to SPR, such as nanowire arrays (24), mechanical (25), or optical (26) resonators, are promising methods for generating quantitative kinetic data, but the throughput of these platforms remains severely limited.…”

mentioning

confidence: 99%

Massively parallel measurements of molecular interaction kinetics on a microfluidic platform

Geertz

Shore

Maerkl

2012

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

103

View full text Add to dashboard Cite

Quantitative biology requires quantitative data. No high-throughput technologies exist capable of obtaining several hundred independent kinetic binding measurements in a single experiment. We present an integrated microfluidic device (k-MITOMI) for the simultaneous kinetic characterization of 768 biomolecular interactions. We applied k-MITOMI to the kinetic analysis of transcription factor (TF)-DNA interactions, measuring the detailed kinetic landscapes of the mouse TF Zif268, and the yeast TFs Tye7p, Yox1p, and Tbf1p. We demonstrated the integrated nature of k-MITOMI by expressing, purifying, and characterizing 27 additional yeast transcription factors in parallel on a single device. Overall, we obtained 2,388 association and dissociation curves of 223 unique molecular interactions with equilibrium dissociation constants ranging from 2 × 10 −6 M to 2 × 10 −9 M, and dissociation rate constants of approximately 6 s −1 to 8.5 × 10 −3 s −1 . Association rate constants were uniform across 3 TF families, ranging from 3.7 × 10 6 M −1 s −1 to 9.6 × 10 7 M −1 s −1 , and are well below the diffusion limit. We expect that k-MITOMI will contribute to our quantitative understanding of biological systems and accelerate the development and characterization of engineered systems.biochemistry | biophysics | systems biology S ystems and synthetic biology, as well as the computational models and engineering-based approaches they employ, rely heavily on quantitative data (1, 2). Thus far, efforts in systems biology have mainly focused on cataloging and mapping genomes and proteomes. Genome sequencing and gene expression analysis have provided insight into genome architecture (3-6), and functional genomics approaches, including high-throughput protein-based methods (7-15), mapped network topologies.Although the number of known protein-protein and protein-DNA interactions is already substantial, the information describing such networks is predominantly qualitative and binary in nature. It is also becoming clear that network topologies alone are not sufficient to model complex biological processes. Precise quantitative information describing every interaction in a network would be tremendously valuable (2), yet binding affinities are known for only a small fraction of interactions (16, 17) and kinetic information hardly exists at all. This dearth of quantitative interaction data is due to a lack of high-throughput technologies capable of measuring kinetic rates of biomolecular interactions. Current methods used for kinetic rate measurements are generally based on surface plasmon resonance (SPR) (18) such as BioRad's ProteOn XPR36 6 × 6 array system, which measures 36 interactions in a single run. SPR-based measurements have been integrated with microfluidic devices (19, 20) to achieve higher degrees of parallelization (21). Yet proof of concept demonstrations have made use of only a small fraction of the proposed throughput and often restrict their measurements to protein-antibody interactions with high affinities and long half-lives...

show abstract

Different Approaches to Develop Nanosensors for Diagnosis of Diseases

et al. 2020

View full text Add to dashboard Cite

The success of clinical treatments is highly dependent on early detection and much research has been conducted to develop fast, efficient, and precise methods for this reason. Conventional methods relying on nonspecific and targeting probes are being outpaced by so‐called nanosensors. Over the last two decades a variety of activatable sensors have been engineered, with a great diversity concerning the operating principle. Therefore, this review delineates the achievements made in the development of nanosensors designed for diagnosis of diseases.

show abstract

In situ real-time monitoring of biomolecular interactions based on resonating microcantilevers immersed in a viscous fluid

Cited by 68 publications

References 18 publications

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

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

Massively parallel measurements of molecular interaction kinetics on a microfluidic platform

Different Approaches to Develop Nanosensors for Diagnosis of Diseases

Contact Info

Product

Resources

About