Probing biomolecular interaction forces using an anharmonic acoustic technique for selective detection of bacterial spores.

Receptor-based detection of pathogens often suffers from non-specific interactions, and as most detection techniques cannot distinguish between affinities of interactions, false positive responses remain a plaguing reality. Here, we report an anharmonic acoustic based method of detection that addresses the inherent weakness of current ligand dependant assays. Spores of Bacillus subtilis (Bacillus anthracis simulant) were immobilized on a thickness-shear mode AT-cut quartz crystal functionalized with anti-spore antibody and the sensor was driven by a pure sinusoidal oscillation at increasing amplitude. Biomolecular interaction forces between the coupled spores and the accelerating surface caused a nonlinear modulation of the acoustic response of the crystal. In particular, the deviation in the third harmonic of the transduced electrical response versus oscillation amplitude of the sensor (signal) was found to be significant. Signals from the specifically-bound spores were clearly distinguishable in shape from those of the physisorbed streptavidin-coated polystyrene microbeads. The analytical model presented here enables estimation of the biomolecular interaction forces from the measured response. Thus, probing biomolecular interaction forces using the described technique can quantitatively detect pathogens and distinguish specific from non-specific interactions, with potential applicability to rapid point-of-care detection. This also serves as a potential tool for rapid force-spectroscopy, affinity-based biomolecular screening and mapping of molecular interaction networks.

Probing biomolecular interaction forces using an anharmonic acoustic technique for selective detection of bacterial spores

Receptor-based detection of pathogens often suffers from non-specific interactions, and as most detection techniques cannot distinguish between affinities of interactions, false positive responses remain a plaguing reality. Here, we report an anharmonic acoustic based method of detection that addresses the inherent weakness of current ligand dependant assays. Spores of Bacillus subtilis (Bacillus anthracis simulant) were immobilized on a thickness-shear mode AT-cut quartz crystal functionalized with anti-spore antibody and the sensor was driven by a pure sinusoidal oscillation at increasing amplitude. Biomolecular interaction forces between the coupled spores and the accelerating surface caused a nonlinear modulation of the acoustic response of the crystal. In particular, the deviation in the third harmonic of the transduced electrical response versus oscillation amplitude of the sensor (signal) was found to be significant. Signals from the specifically-bound spores were clearly distinguishable in shape from those of the physisorbed streptavidin-coated polystyrene microbeads. The analytical model presented here enables estimation of the biomolecular interaction forces from the measured response. Thus, probing biomolecular interaction forces using the described technique can quantitatively detect pathogens and distinguish specific from non-specific interactions, with potential applicability to rapid point-of-care detection. This also serves as a potential tool for rapid force-spectroscopy, affinity-based biomolecular screening and mapping of molecular interaction networks. © 2011 Elsevier B.V.

Impedance mismatch: some differences between the way humans and robots control interaction forces

In over forty years of research robots have made very little progress still largely confined to industrial manufacture and cute toys, yet in the same period computing has followed Moores Law where the capacity double roughly every two years. So why is there no Moores Law for robots? Two areas stand out as worthy of research to speedup progress. The first is to get a greater understanding of how human and animal brains control movement, the second to build a new generation of robots that have greater haptic sense, that is a better ability to adapt to the environment as it is encountered. A remarkable property of the cognitive-motor system in humans and animals is that it is slow. Recognising an object may take 250 mS, a reaction time of 150 mS is considered fast. Yet despite this slow system we are well designed to allow contact with the world in a variety of ways. We can anticipate an encounter, use the change of force as a means of communication and ignore sensory cues when they are not relevant. A better understanding of these process has allowed us to build haptic interfaces to mimic the interaction. Emerging from this understanding are new ways to control the contact between robots, the user and the environment. Rehabilitation robotics has all the elements in the subject to not only enable and change the lives of people with disabilities, but also to facilitate revolution change in classic robotics.

The electrochemical surface forces apparatus : the effect of surface roughness, electrostatic surface potentials, and anodic oxide growth on interaction forces, and friction between dissimilar surfaces in aqueous solutions

We present a newly designed electrochemical surface forces apparatus (EC-SFA) that allows control and measurement of surface potentials and interfacial electrochemical reactions with simultaneous measurement of normal interaction forces (with nN resolution), friction forces (with μN resolution), and distances (with Å resolution) between apposing surfaces. We describe three applications of the developed EC-SFA and discuss the wide-range of potential other applications. In particular, we describe measurements of (1) force–distance profiles between smooth and rough gold surfaces and apposing self-assembled monolayer-covered smooth mica surfaces; (2) the effective changing thickness of anodically growing oxide layers with Å-accuracy on rough and smooth surfaces; and (3) friction forces evolving at a metal–ceramic contact, all as a function of the applied electrochemical potential. Interaction forces between atomically smooth surfaces are well-described using DLVO theory and the Hogg–Healy–Fuerstenau approximation for electric double layer interactions between dissimilar surfaces, which unintuitively predicts the possibility of attractive double layer forces between dissimilar surfaces whose surface potentials have similar sign, and repulsive forces between surfaces whose surface potentials have opposite sign. Surface roughness of the gold electrodes leads to an additional exponentially repulsive force in the force–distance profiles that is qualitatively well described by an extended DLVO model that includes repulsive hydration and steric forces. Comparing the measured thickness of the anodic gold oxide layer and the charge consumed for generating this layer allowed the identification of its chemical structure as a hydrated Au(OH)3 phase formed at the gold surface at high positive potentials. The EC-SFA allows, for the first time, one to look at complex long-term transient effects of dynamic processes (e.g., relaxation times), which are also reflected in friction forces while tuning electrochemical surface potentials.

Spinal circuits can accommodate interaction torques during multijoint limb movements

The dynamic interaction of limb segments during movements that involve multiple joints creates torques in one joint due to motion about another. Evidence shows that such interaction torques are taken into account during the planning or control of movement in humans. Two alternative hypotheses could explain the compensation of these dynamic torques. One involves the use of internal models to centrally compute predicted interaction torques and their explicit compensation through anticipatory adjustment of descending motor commands. The alternative, based on the equilibrium-point hypothesis, claims that descending signals can be simple and related to the desired movement kinematics only, while spinal feedback mechanisms are responsible for the appropriate creation and coordination of dynamic muscle forces. Partial supporting evidence exists in each case. However, until now no model has explicitly shown, in the case of the second hypothesis, whether peripheral feedback is really sufficient on its own for coordinating the motion of several joints while at the same time accommodating intersegmental interaction torques. Here we propose a minimal computational model to examine this question. Using a biomechanics simulation of a two-joint arm controlled by spinal neural circuitry, we show for the first time that it is indeed possible for the neuromusculoskeletal system to transform simple descending control signals into muscle activation patterns that accommodate interaction forces depending on their direction and magnitude. This is achieved without the aid of any central predictive signal. Even though the model makes various simplifications and abstractions compared to the complexities involved in the control of human arm movements, the finding lends plausibility to the hypothesis that some multijoint movements can in principle be controlled even in the absence of internal models of intersegmental dynamics or learned compensatory motor signals.

Forces between bilayers of cetyltrimethylammonium bromide in micellar solutions

A direct force-measuring technique has been used to study the interaction forces between adsorbed CTAB (cetyltrimethylammonium bromide) bilayers at concentrations well above the CMC (critical micelle concentration). An analysis of these results based on the Poisson-Boltzmann equations leads to the conclusion that CTAB micelles and adsorbed bilayers are about 22(±4)% dissociated. The apparent agreement of bilayer and micellar ion binding parameters raises an important challenge for theories of double-layer interactions. In addition, the double-layer decay lengths observed in these micellar solutions appear to be due entirely to the dissociated bromide and free CTA+ ions, with no apparent contribution from charged micelles.

Effect of surface roughness and electrostatic surface potentials on forces between dissimilar surfaces in aqueous solution

The first surface force measurements under electrochemical potential control between a metal and a ceramic surface across a liquid medium (water) are reported. Our experiments also investigate and reveal how increasing levels of surface roughness and dissimilarity between the potentials of the interacting surfaces influence the strength and range of electric double layer, van der Waals, hydration, and steric forces and how this contributes to deviations from DLVO theory at small distances within aqueous solution.

A numerical program for Railway vehicle-track-structure dynamic interaction using a modal substructuring approach

This work presents a program for simulations of vehicle-track and vehicle-trackstructure dynamic interaction . The method used is computationally efficient in the sense that a reduced number of coordinates is sufficient and doesn’t require high efficiency computers. The method proposes a modal substructuring approach of the system by modelling rails , sleepers and underlying structure with modal coordinates, the vehicle with physical lumped elements coordinates and by introducing interconnection elements between these structures (wheel-rail contact, railpads and ballast) by means of their interaction forces. The Frequency response function (FRF) is also calculated for both cases of track over a structure (a bridge, a viaduct ...) and for the simple vehicle-track program; for each case the vehicle effect on the FRF is then analyzed through the comparison of the FRFs obtained introducing or not a simplified vehicle on the system.

A THEORETICAL STUDY OF INTERACTION OF NANOPARTICLES WITH BIOMOLECULE

Many types of materials at nanoscale are currently being used in everyday life. The production and use of such products based on engineered nanomaterials have raised concerns of the possible risks and hazards associated with these nanomaterials. In order to evaluate and gain a better understanding of their effects on living organisms, we have performed first-principles quantum mechanical calculations and molecular dynamics simulations. Specifically, we will investigate the interaction of nanomaterials including semiconducting quantum dots and metallic nanoparticles with various biological molecules, such as dopamine, DNA nucleobases and lipid membranes. Firstly, interactions of semiconducting CdSe/CdS quantum dots (QDs) with the dopamine and the DNA nucleobase molecules are investigated using similar quantum mechanical approach to the one used for the metallic nanoparticles. A variety of interaction sites are explored. Our results show that small-sized Cd4Se4 and Cd4S4 QDs interact strongly with the DNA nucleobase if a DNA nucleobase has the amide or hydroxyl chemical group. These results indicate that these QDs are suitable for detecting subcellular structures, as also reported by experiments. The next two chapters describe a preparation required for the simulation of nanoparticles interacting with membranes leading to accurate structure models for the membranes. We develop a method for the molecular crystalline structure prediction of 1,2-Dimyristoyl-sn-glycero-3-phosphorylcholine (DMPC), 1,2-Dimyristoyl-sn-glycero-3-phosphorylethanolamine (DMPE) and cyclic di-amino acid peptide using first-principles methods. Since an accurate determination of the structure of an organic crystal is usually an extremely difficult task due to availability of the large number of its conformers, we propose a new computational scheme by applying knowledge of symmetry, structural chemistry and chemical bonding to reduce the sampling size of the conformation space. The interaction of metal nanoparticles with cell membranes is finally carried out by molecular dynamics simulations, and the results are reported in the last chapter. A new force field is developed which accurately describes the interaction forces between the clusters representing small-sized metal nanoparticles and the lipid bilayer molecules. The permeation of nanoparticles into the cell membrane is analyzed together with the RMSD values of the membrane modeled by a lipid bilayer. The simulation results suggest that the AgNPs could cause the same amount of deformation as the AuNPs for the dysfunction of the membrane.

Study of gas cavity size hysteresis in a packed bed using DEM

When a high velocity gas jet is introduced into a packed bed a cavity is formed. The size of the cavity shows hysteresis on increasing and decreasing gas flow rates. This hysteresis leads to different cavity sizes at same gas flow rate depending on the bed history. The size of cavity affects the gas flow profiles in the packed bed. In this study the cavity size hysteresis phenomenon has been modeled using discrete element method along with turbulent gas flow. A reasonable agreement has been found between computed and experimental results on cavity size ysteresis. The effect of various parameters, such as nozzle height from the bed bottom and packing height, on the cavity size hysteresis has been studied. It is found that inter-particle interaction forces along with gas drag and bed porosity play an important role in describing the cavity size hysteresis. The injection of gas flow allows the particles to go to an unconstrained state than they were previously in, and their ability to remain in that state, even under decreased gas drag force, leads to the phenomenon of cavity size hysteresis. (c) 2007 Elsevier Ltd. All rights reserved.

Long range interactions between some charged solitons

A procedure is offered for evaluating the forces between classical, charged solitons at large distances. This is employed for the solitons of a complex, scalar two-dimensional field theory with a U(1) symmetry, that leads to a conserved chargeQ. These forces are the analogues of the strong interaction forces. The potential,U(Q, R), is found to be attractive, of long range, and strong when the coupling constants in the theory are small. The dependence ofU(Q, R) onQ, the sum of the charges of the two interacting solitons (Q will refer to isospin in the SU(2) generalisation of the U(1) symmetric theory) is of importance in the theory of strong interactions; group theoretical considerations do not give such information. The interaction obtained here will be the leading term in the corresponding quantum field theory when the coupling-constants are small.

Virus-sized colloid transport in a single pore: Model development and sensitivity analysis

A mathematical model is developed to simulate the transport and deposition of virus-sized colloids in a cylindrical pore throat considering various processes such as advection, diffusion, colloid-collector surface interactions and hydrodynamic wall effects. The pore space is divided into three different regions, namely, bulk, diffusion and potential regions, based on the dominant processes acting in each of these regions. In the bulk region, colloid transport is governed by advection and diffusion whereas in the diffusion region, colloid mobility due to diffusion is retarded by hydrodynamic wall effects. Colloid-collector interaction forces dominate the transport in the potential region where colloid deposition occurs. The governing equations are non-dimensionalized and solved numerically. A sensitivity analysis indicates that the virus-sized colloid transport and deposition is significantly affected by various pore-scale parameters such as the surface potentials on colloid and collector, ionic strength of the solution, flow velocity, pore size and colloid size. The adsorbed concentration and hence, the favorability of the surface for adsorption increases with: (i) decreasing magnitude and ratio of surface potentials on colloid and collector, (ii) increasing ionic strength and (iii) increasing pore radius. The adsorbed concentration increases with increasing Pe, reaching a maximum value at Pe = 0.1 and then decreases thereafter. Also, the colloid size significantly affects particle deposition with the adsorbed concentration increasing with increasing particle radius, reaching a maximum value at a particle radius of 100 nm and then decreasing with increasing radius. System hydrodynamics is found to have a greater effect on larger particles than on smaller ones. The secondary minimum contribution to particle deposition has been found to increase as the favorability of the surface for adsorption decreases. The sensitivity of the model to a given parameter will be high if the conditions are favorable for adsorption. The results agree qualitatively with the column-scale experimental observations available in the literature. The current model forms the building block in upscaling colloid transport from pore scale to Darcy scale using Pore-Network Modeling. (C) 2014 Elsevier By. All rights reserved.

Design and Modeling of an Active Five-Axis Compliant Micromanipulator

This paper presents the design and modeling of an active five-axis compliant micromanipulator whose tip orientation can be independently controlled by large angles about two axes and the tip-position can be controlled in three dimensions. These features enable precise control of the contact point of the tip and the tip-sample interaction forces with three-dimensional nanoscale objects, including those features that are conventionally inaccessible. Control of the tip-motion is realized by means of electromagnetic actuation combined with a novel kinematic and structural design of the micromanipulator, which, in addition, also ensures compatibility with existing high-resolution motion-measurement systems. The design and analysis of the manipulator structure and those of the actuation system are first presented. Quasi-static and dynamic lumped-parameter (LP) models are then derived for the five-axis compliant micromanipulator. Finite element (FE) analysis is employed to validate these models, which are subsequently used to study the effects of tip orientation on the mechanical characteristics of the five-axis micromanipulator. Finally, a prototype of the designed five-axis manipulator is fabricated by means of focused ion-beam milling (FIB).

Correlation equations for average deposition rate coefficients of nanoparticles in a cylindrical pore

Nanoparticle deposition behavior observed at the Darcy scale represents an average of the processes occurring at the pore scale. Hence, the effect of various pore-scale parameters on nanoparticle deposition can be understood by studying nanoparticle transport at pore scale and upscaling the results to the Darcy scale. In this work, correlation equations for the deposition rate coefficients of nanoparticles in a cylindrical pore are developed as a function of nine pore-scale parameters: the pore radius, nanoparticle radius, mean flow velocity, solution ionic strength, viscosity, temperature, solution dielectric constant, and nanoparticle and collector surface potentials. Based on dominant processes, the pore space is divided into three different regions, namely, bulk, diffusion, and potential regions. Advection-diffusion equations for nanoparticle transport are prescribed for the bulk and diffusion regions, while the interaction between the diffusion and potential regions is included as a boundary condition. This interaction is modeled as a first-order reversible kinetic adsorption. The expressions for the mass transfer rate coefficients between the diffusion and the potential regions are derived in terms of the interaction energy profile. Among other effects, we account for nanoparticle-collector interaction forces on nanoparticle deposition. The resulting equations are solved numerically for a range of values of pore-scale parameters. The nanoparticle concentration profile obtained for the cylindrical pore is averaged over a moving averaging volume within the pore in order to get the 1-D concentration field. The latter is fitted to the 1-D advection-dispersion equation with an equilibrium or kinetic adsorption model to determine the values of the average deposition rate coefficients. In this study, pore-scale simulations are performed for three values of Peclet number, Pe = 0.05, 5, and 50. We find that under unfavorable conditions, the nanoparticle deposition at pore scale is best described by an equilibrium model at low Peclet numbers (Pe = 0.05) and by a kinetic model at high Peclet numbers (Pe = 50). But, at an intermediate Pe (e.g., near Pe = 5), both equilibrium and kinetic models fit the 1-D concentration field. Correlation equations for the pore-averaged nanoparticle deposition rate coefficients under unfavorable conditions are derived by performing a multiple-linear regression analysis between the estimated deposition rate coefficients for a single pore and various pore-scale parameters. The correlation equations, which follow a power law relation with nine pore-scale parameters, are found to be consistent with the column-scale and pore-scale experimental results, and qualitatively agree with the colloid filtration theory. These equations can be incorporated into pore network models to study the effect of pore-scale parameters on nanoparticle deposition at larger length scales such as Darcy scale.