Physics of Nanomechanical Biosensing on Cantilever Arrays

Abstract

Living systems that transform biomolecular reactions at the nanoscale into mechanical work at multiple nano-, meso-and macroscopic length scales have inspired the advancing fields of nanotechnology. [1][2][3][4][5][6][7] Cantilever sensors, which integrate 'topdown' miniaturized MEMS devices with 'bottom up' selfassembly of biomolecules, offer the unique ability to convert biomolecular reactions occurring on one side of the cantilever into mesoscopic bending motion for biosensing and smart nanorobotic applications. [8] The differential mode (defined as the bending of the 'active' cantilever minus the bending of an in situ reference cantilever coated with an non-reactive coating) has been shown to be essential for biospecific analysis and exploited experimentally to detect pH, [9,10] sequence-specific DNA hybridization with single nucleotide polymorphisms, [11][12][13][14][15][16][17] and protein recognition. [18][19][20][21] However, further advances have been limited by a lack of theory underlying the origins of surface stress. For example, both the direction and amplitude of cantilever motion have experimentally been found to depend on the length of the bio-molecule reacting on the cantilever. [11][12][13][14][15][16][17] These effects cannot be explained by the traditional theory developed for macroscopic systems, which ignores the physical properties of the active layer. Therefore, new theoretical approaches need to be developed. Moreover the development of a fundamental theory to identify the key 'figures of merit' will aid the rational design of new coatings and device geometries with significantly improved detection sensitivities for biosensing applications. The challenge for theory is that these complex BioMEMS devices are essentially multiscale systems in which molecularlevel signals are transduced to mesoscopic elements, to allow the readout by macroscopic methods. The multilayer structure of cantilever sensors comprises typically a silicon cantilever (500 mm long, 100 mm wide and 1 mm thick), thin gold films (20 nm), a self-assembled monolayer (SAM) (1-2 nm thick) all in a buffer solution environment. Each of these layers requires different modeling techniques which together span traditionally distinct areas, namely material science, solid-state physics, organic chemistry and soft matter theory, respectively. Each of these techniques tends to impose different boundary conditions and approximations, which often break down at the interfaces. They often assume ideal properties, for example, uniformity and flatness, which can differ significantly from experimentally prepared samples.[22] Therefore, the challenge is to develop a unified multiscale model of nanomechanical sensors and to test the assumptions of this model with experiments. Here, we report the first quantitative multiscale model to describe the transduction of specific biochemical reactions into micromechanical cantilever bending motion. Our approach can be divided into five steps (see Experimental Section for more details):(i) Firstly, we hav...

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

“…We expect that, owing to recent advances in nanotechnology, it will be possible to fabricate a nanocantilever and/or nanoresonator which can be suitable for validating the relationship that is currently available from molecular/multiscale simulations described in Section 5.3.1. For example, there has recently been an experimental effort [334] to validate insights into the role of intermolecular interactions between adsorbates on the bending deflection motion of microcantilevers, which were obtained from multiscale simulations [335]. We anticipate that the atomic adsorption onto nanoresonators and/or nanocantilevers can be considered as a model system for experimental validation, because interatomic interactions for adsorbed atoms can be straightforwardly described by non-bonded interactions such as van der Waals interactions and/or electrostatic interactions [191,307,308] (see also discussions in Section 5.3.1).…”

Optimization of Capacitive Membrane Sensors for Surface-Stress-Based Measurements

“…It is commonly assumed that if the surface coverage is uniformly dispersed, the surface stress induced by the adsorption exhibits a non-linear dependence on the surface coverage, and it steeply increases when the coverage is near saturation [1], [17], [18]. However, at low concentration of target molecules, or when the target molecules or proteins are large, the distribution of the coverage might be randomly dispersed or just accumulated in one area [18], [19].…”

Tackling reproducibility in microcantilever biosensors: a statistical approach for sensitive and specific end-point detection of immunoreactions

“…The surface density of biomolecular receptors plays a crucial role in the sensitivity and specificity of surface-stress based nanomechanical biosensors 18,[21][22][23]27 . Here, we characterized the cantilever response for three antibody concentrations: 5 µg/ml, 50 µg/ml and 250 µg/mL.…”

“…In this work, we examine the capability of micro-and nanocantilever biosensors in the static mode [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] for end point label-free immunoassays. In these devices, molecular recognition between the analyte and the receptor monolayer anchored on one side of a tiny cantilever induces a nanoscale bending as a consequence of the surface stress variation on the functionalized surface 32 .…”