Biosensors based on nanomechanical systems

Abstract

The advances in micro-and nanofabrication technologies are enabling increasingly smaller mechanical transducers capable of detecting the forces, motion, mechanical properties and masses that emerge in biomolecular interactions and fundamental biological processes. Thus, biosensors based on nanomechanical systems have gained considerable relevance in the last decade. This review provides insight into the mechanical phenomena that occur in suspended mechanical structures when either biological adsorption or interactions take place on their surface. This review guides the reader through the parameters that change as a consequence of biomolecular adsorption: mass, surface stress, effective Young's modulus and viscoelasticity.The mathematical background needed to correctly interpret the output signals from nanomechanical biosensors is also outlined here. Other practical issues reviewed are the immobilization of bioreceptor molecules on the surface of nanomechanical sensors and methods to attain that in large arrays of sensors. We describe then some relevant realizations of biosensor devices based on nanomechanical systems that harness some of the mechanical effects cited above. We finally discuss the intrinsic detection limits of the devices and the limitation that arises from non-specific adsorption.2

Physics of Nanomechanical Spectrometry of Viruses

“…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.…”

“…(2)), equation (1) largely simplifies, and the fractional resonance frequency shift for small adsorbates can be expressed as the sum of a negative term related to the inertial effect and a positive term related to the bending stiffness effect, respectively given by (Supplementary Section S2) 1,12 , Df n f n b…”

“…where V is the volume, m is the mass, E is the Young's modulus; the subscripts c and a denote the cantilever and the adsorbate, respectively; f is the x-coordinate normalized by the beam length (L), thereby f 0~x 0 L ; y n and b n are the vibration shape (eigenfunctions) and eigenvalues of the n th mode obtained from the solution of the Euler-Bernoulli beam equation 1 (Supplementary Section S2), respectively. The eigenfunctions are normalized so that…”

Hydration Induced Stress on DNA Monolayers Grafted on Microcantilevers

“…1,2 In depth knowledge about the conformations of such selfassembled monolayers (SAMs) is crucial to understand and control the performance of any surface based nucleic acid sensor. Particularly, the intriguing mechanical properties of these films on microcantilevers have been harnessed to develop labelfree nanomechanical sensors for DNA detection.…”

“…Particularly, the intriguing mechanical properties of these films on microcantilevers have been harnessed to develop labelfree nanomechanical sensors for DNA detection. 2 The changes in surface stress induced by the hybridization of probe-target strands have been followed in buffer solutions to detect the hybridization in real time and with sufficiently high sensitivity as to avoid the need of pre-amplification steps in complex samples, such as cell lysate. 3,4 Hydration driven structural changes in DNA have recently gained further attention for the generation of responsive biomaterials.…”