Atomic force microscope (AFM) is an invaluable tool for measurement of pico-Newton to nano-Newton levels of interaction forces in liquid. As such, it is widely used to measure single-molecular interaction forces through dynamic force spectroscopy. In this technique, the interaction force spectra between a specimen on the sharp tip of the cantilever and another specimen on the substrate is measured by repeatedly moving the cantilever in and out of contact with the substrate. By varying the loading rate and measuring the bond rupture force or bond lifetime give researchers information about the strength and dissociation rates of non-covalent bonds, which in turn determines the energy barriers to overcome. Commercially available cantilevers can resolve interaction forces as low as 5 pN with 1 kHz bandwidth in fluid. This resolution can be improved to 1 pN by using smaller cantilevers at the expense of microfabrication constraints and sophisticated detection systems. The pulling speed of the cantilever, which determines the loading rate of the bonds, is limited to the point where the hydrodynamic drag force becomes comparable to the level of the molecular interaction force. This level is around 10 um/s for most cantilevers while higher pulling speeds are required for complete understanding of force spectra. Thus, novel actuators that allow higher loading rates with minimal hydrodynamic drag forces on the cantilevers, and fast, sensitive force sensors with simple detection systems are highly desirable. This dissertation presents the research efforts for the development of membrane-based active probe structures with electrostatic actuation and integrated diffraction-based optical interferometric force detection for single-molecular force measurements. Design, microfabrication and characterization of the probes are explained in detail. A setup including optics and electronics for experimental characterization and biological experiments with the probes membranes is also presented. Finally, biological experiments are included in this dissertation. The "active" nature of the probe is because of the integrated, parallel-plate type electrostatic actuator. The actuation range of the membrane is controlled with the gap height between the membrane and the substrate. Within this range it is possible to actuate the membrane fast, with a speed limited by the membrane dynamics with negligible hydrodynamic drag. Actuating these membrane probes and using a cantilever coupled to the membrane, fast pulling experiments with an order of magnitude faster than achieved by regular AFM systems are demonstrated. The displacement noise spectral density for the probe was measured to be below 10 fm/rtHz for frequencies as low as 3 Hz with differential readout scheme. This noise floor provides a force sensitivity of 0.3 - 3 pN with 1 kHz bandwidth using membranes with spring constants of 1 - 10 N/m. This low inherent noise has a potential to probe wide range of biomolecules. The probes have been demonstrated for fast-pulling and high-resolution force sensing. Feasibility for high throughput parallel operation has been explored. Unique capabilities of the probes such as electrostatic spring constant tuning and thermal drift cancellation in AFM are also presented in this dissertation.

Malgré un rôle important en physique, biologie et dans les processus industriels tels l’agroalimentaire et la dépollution de l’eau, la dynamique d'une particule colloïdale à proximité d'une interface fluide et ses interactions avec l’interface sont des phénomènes physiques encore débattus.Dans cette thèse, nous explorons la dynamique et l'interaction de particules colloïdales individuelles à proximité d'une interface air-eau à l’équilibre thermique.Afin de mener cette étude sans perturber le système expérimental, nous avons conçu et construit un microscope interférentiel à double onde adapté à l'interface air-eau. Contrairement à d'autres techniques expérimentales, notre configuration permet la mesure précise de la distance absolue entre particule l'interface sans nécessiter d’étalonnage ou d’hypothèse sur l'emplacement de l'interface. Nous avons ainsi pu obtenir des trajectoires hautement résolues de particules en 3D proches de l'interface, permettant la mesure précise des diffusions proche de l’interface et des interactions particules-interface.Le système montre deux profils d’énergie potentielle différents. Deux distances d’équilibre particule-interface sont ainsi observées. La plus grande peut être expliquée par la compétition des interactions de Van der Waals et électrostatiques avec la pesanteur. La distance d’équilibre plus courte ne peut s’expliquer que par la présence d’une interaction attractive supplémentaire. Les origines possibles de cette interaction sont discutées.En utilisant une nouvelle méthode d'analyse des déplacements quadratiques moyens des particules dans un potentiel générique, nous avons pu accéder aux coefficients de friction visqueuse des particules en fonction de la distance à l'interface. De manière singulière, l’interface air-eau se comporte comme une paroi liquide pour le mouvement des particules parallèlement à l’interface et comme une paroi solide pour le mouvement des particules perpendiculaire à l’interface. Ce résultat expérimental peut être partiellement rationalisé en considérant des modèles récents basés sur l’incompressibilité de surface. Cependant, certaines différences entre les expériences et les théories demeurent. Les coefficients de friction visqueuse sont plus importants que les prédictions hydrodynamiques et dépendent de la charge électrique des particules, ce qui suggère un possible rôle des phénomènes électrocinétiques.Enfin, le piégeage des particules à l'interface air-eau et leur angle de contact ont été mesurés tout en modifiant la force ionique de la solution aqueuse et en faisant varier l‘état de surface des colloïdes. / Despite the relevance to environmental, biological and industrial processes, the motion of a colloidal particle close to a fluid interface and the way it interacts with the water surface are still largely elusive and intriguing physical phenomena.In this thesis, we explore the motion dynamics and the interaction of individual colloidal particles close to an air-water interface in thermal equilibrium.In order to investigate them without perturbing or altering the experimental system, we designed and built a dual-wave reflection interference microscope working with an air-water interface geometry. Contrary to other established experimental techniques, our set-up allows accurate measurements of the absolute particle-interface distance and thus does not require any calibration or assumption to know the location of the interface. Highly resolved 3D particle trajectories close to the interface were obtained, from which information on particle diffusion close to the interface and particle-interface interactions are obtained.The system shows two different potential energy landscapes resulting in two different equilibrium particle-interface distances. The larger one can be fairly explained by Van der Waals and electrostatic interactions combined with gravity. The shorter one highlights the existence of an unexpected additional attractive interaction. The possible origins of such an interaction are discussed.Using a method of analysis of the particle mean square displacements in a generic potential we developed, we were able to access to particle drag coefficients as a function of the distance from the interface. Peculiarly, the air-water interface acts as a slip boundary for the particle motion parallel to the interface and as a no-slip boundary for the particle motion perpendicular to the interface. This experimental result can be partially rationalized considering recent models based on surface incompressibility. However, some discrepancies between experiments and theories remain. Experimental drag coefficients are larger than the hydrodynamic predictions and depend on the particle electrical charge, pointing therefore to a possible role of electrokinetic phenomena.Finally, the particle trapping at the air-water interface and its contact angle were observed while tuning the ionic strength of the aqueous solution and varying the surface state of the colloids.

Extracellular neuroelectronic interfacing has important applications in the fields of neural prosthetics, biological computation and whole-cell biosensing for drug screening and toxin detection. While the field of neuroelectronic interfacing holds great promise, the recording of high-fidelity signals from extracellular devices has long suffered from the problem of low signal-to-noise ratios and changes in signal shapes due to the presence of highly dispersive dielectric medium in the neuron-microelectrode cleft. This has made it difficult to correlate the extracellularly recorded signals with the intracellular signals recorded using conventional patch-clamp electrophysiology. For bringing about an improvement in the signalto-noise ratio of the signals recorded on the extracellular microelectrodes and to explore strategies for engineering the neuron-electrode interface there exists a need to model, simulate and characterize the cell-sensor interface to better understand the mechanism of signal transduction across the interface. Efforts to date for modeling the neuron-electrode interface have primarily focused on the use of point or area contact linear equivalent circuit models for a description of the interface with an assumption of passive linearity for the dynamics of the interfacial medium in the cell-electrode cleft. In this dissertation, results are presented from a nonlinear dynamic characterization of the neuroelectronic junction based on Volterra-Wiener modeling which showed that the process of signal transduction at the interface may have nonlinear contributions from the interfacial medium. An optimization based study of linear equivalent circuit models for representing signals recorded at the neuron-electrode interface subsequently iv proved conclusively that the process of signal transduction across the interface is indeed nonlinear. Following this a theoretical framework for the extraction of the complex nonlinear material parameters of the interfacial medium like the dielectric permittivity, conductivity and diffusivity tensors based on dynamic nonlinear Volterra-Wiener modeling was developed. Within this framework, the use of Gaussian bandlimited white noise for nonlinear impedance spectroscopy was shown to offer considerable advantages over the use of sinusoidal inputs for nonlinear harmonic analysis currently employed in impedance characterization of nonlinear electrochemical systems. Signal transduction at the neuron-microelectrode interface is mediated by the interfacial medium confined to a thin cleft with thickness on the scale of 20-110 nm giving rise to Knudsen numbers (ratio of mean free path to characteristic system length) in the range of 0.015 and 0.003 for ionic electrodiffusion. At these Knudsen numbers, the continuum assumptions made in the use of Poisson-Nernst-Planck system of equations for modeling ionic electrodiffusion are not valid. Therefore, a lattice Boltzmann method (LBM) based multiphysics solver suitable for modeling ionic electrodiffusion at the mesoscale neuron-microelectrode interface was developed. Additionally, a molecular speed dependent relaxation time was proposed for use in the lattice Boltzmann equation. Such a relaxation time holds promise for enhancing the numerical stability of lattice Boltzmann algorithms as it helped recover a physically correct description of microscopic phenomena related to particle collisions governed by their local density on the lattice. Next, using this multiphysics solver simulations were carried out for the charge relaxation dynamics of an electrolytic nanocapacitor with the intention of ultimately employing it for a simulation of the capacitive coupling between the neuron and the v planar microelectrode on a microelectrode array (MEA). Simulations of the charge relaxation dynamics for a step potential applied at t = 0 to the capacitor electrodes were carried out for varying conditions of electric double layer (EDL) overlap, solvent viscosity, electrode spacing and ratio of cation to anion diffusivity. For a large EDL overlap, an anomalous plasma-like collective behavior of oscillating ions at a frequency much lower than the plasma frequency of the electrolyte was observed and as such it appears to be purely an effect of nanoscale confinement. Results from these simulations are then discussed in the context of the dynamics of the interfacial medium in the neuron-microelectrode cleft. In conclusion, a synergistic approach to engineering the neuron-microelectrode interface is outlined through a use of the nonlinear dynamic modeling, simulation and characterization tools developed as part of this dissertation research.