61 research outputs found

    Dual integrated actuators for extended range high speed atomic force microscopy

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    Cataloged from PDF version of article.A flexible system for increasing the throughput of the atomic force microscope without sacrificing imaging range is presented. The system is based on a nested feedback loop which controls a micromachined cantilever that contains both an integrated piezoelectric actuator and an integrated thermal actuator. This combination enables high speed imaging (2 mm/s) over an extended range by utilizing the piezoelectric actuator’s high bandwidth (15 kHz) and thermal actuator’s large response (300 nm/V). A constant force image, where the sample topography exceeds the range of the piezoelectric actuator alone, is presented. It has also been demonstrated that the deflection response of the thermal actuator can be linearized and controlled with an integrated diode. © 1999 American Institute of Physic

    Scan speed control for tapping mode SPM

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    In order to increase the imaging speed of a scanning probe microscope in tapping mode, we propose to use a dynamic controller on 'parachuting' regions. Furthermore, we propose to use variable scan speed on 'upward step' regions, with the speed determined by the error signal of the closed-loop control. We offer line traces obtained on a calibration grating with 25-nm step height, using both standard scanning and our scanning method, as experimental evidence

    Parallel atomic force microscopy with optical interferometric detection

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    Cataloged from PDF version of article.We have developed an atomic force microscope that uses interferometry for parallel readout of a cantilever array. Each cantilever contains a phase sensitive diffraction grating consisting of a reference and movable set of interdigitated fingers. As a force is applied to the tip, the movable set is displaced and the intensity of the diffracted orders is altered. The order intensity from each cantilever is measured with a custom array of siliconphotodiodes with integrated complementary metal–oxide–semiconductor amplifiers. We present images from five cantilevers acquired in the constant height mode that reveal surface features 2 nm in height. The interdigital method for cantilever array readout is scalable, provides angstrom resolution, and is potentially simpler to implement than other methods. © 2001 American Institute of Physic

    High-speed tapping mode imaging with active Q control for atomic force microscopy

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    Cataloged from PDF version of article.The speed of tapping mode imaging with the atomic force microscope(AFM) has been increased by over an order of magnitude. The enhanced operation is achieved by (1) increasing the instrument’s mechanical bandwidth and (2) actively controlling the cantilever’s dynamics. The instrument’s mechanical bandwidth is increased by an order of magnitude by replacing the piezotube z-axis actuator with an integrated zinc oxide (ZnO)piezoelectric cantilever. The cantilever’s dynamics are optimized for high-speed operation by actively damping the quality factor (Q) of the cantilever. Active damping allows the amplitude of the oscillating cantilever to respond to topography changes more quickly. With these two advancements, 80μm×80 μm high-speed tapping mode images have been obtained with a scan frequency of 15 Hz. This corresponds to a tip velocity of 2.4 mm/s. © 2000 American Institute of Physic

    Dynamic force spectroscopy of parallel individual mucin1-antibody bonds

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    We used atomic force microscopy (AFM) to measure the binding forces between Mucin1 (MUC1) peptide and a single chain antibody fragment (scFv) selected from a scFv library screened against MUC1. This binding interaction is central to the design of the molecules for targeted delivery of radioimmunotherapeutic agents for prostate and breast cancer treatment. Our experiments separated the specific binding interaction from non-specific interactions by tethering the antibody and MUC1 molecules to the AFM tip and sample surface with flexible polymer spacers. Rupture force magnitude and elastic characteristics of the spacers allowed identification of the bond rupture events corresponding to different number of interacting proteins. We used dynamic force spectroscopy to estimate the intermolecular potential widths and equivalent thermodynamic off rates for mono-, bi-, and tri-valent interactions. Measured interaction potential parameters agree with the results of molecular docking simulation. Our results demonstrate that an increase of the interaction valency leads to a precipitous decline in the dissociation rate. Binding forces measured for mono and multivalent interactions match the predictions of a Markovian model for the strength of multiple uncorrelated bonds in parallel configuration. Our approach is promising for comparison of the specific effects of molecular modifications as well as for determination of the best configuration of antibody-based multivalent targeting agents

    Single-Molecule Force Spectroscopy: Experiments, Analysis, and Simulations

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    International audienceThe mechanical properties of cells and of subcellular components are important to obtain a mechanistic molecular understanding of biological processes. The quantification of mechanical resistance of cells and biomolecules using biophysical methods matured thanks to the development of nanotechnologies such as optical and magnetic tweezers, the biomembrane force probe and atomic force microscopy (AFM). The quantitative nature of force spectroscopy measurements has converted AFM into a valuable tool in biophysics. Force spectroscopy allows the determination of the forces required to unfold protein domains and to disrupt individual receptor/ligand bonds. Molecular simulation as a computational microscope allows investigation of similar biological processes with an atomistic detail. In this chapter, we first provide a step-by-step protocol of force spectroscopy including sample preparation, measurement and analysis of force spectroscopy using AFM and its interpretation in terms of available theories. Next, we present the background for molecular dynamics (MD) simulations focusing on steered molecular dynamics (SMD) and the importance of bridging of computational tools with experimental technique
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