Array atomic force microscopy for real-time multiparametric analysis.

Nanoscale multipoint structure-function analysis is essential for deciphering the complexity of multiscale biological and physical systems. Atomic force microscopy (AFM) allows nanoscale structure-function imaging in various operating environments and can be integrated seamlessly with disparate probe-based sensing and manipulation technologies. Conventional AFMs only permit sequential single-point analysis; widespread adoption of array AFMs for simultaneous multipoint study is challenging owing to the intrinsic limitations of existing technological approaches. Here, we describe a prototype dispersive optics-based array AFM capable of simultaneously monitoring multiple probe-sample interactions. A single supercontinuum laser beam is utilized to spatially and spectrally map multiple cantilevers, to isolate and record beam deflection from individual cantilevers using distinct wavelength selection. This design provides a remarkably simplified yet effective solution to overcome the optical cross-talk while maintaining subnanometer sensitivity and compatibility with probe-based sensors. We demonstrate the versatility and robustness of our system on parallel multiparametric imaging at multiscale levels ranging from surface morphology to hydrophobicity and electric potential mapping in both air and liquid, mechanical wave propagation in polymeric films, and the dynamics of living cells. This multiparametric, multiscale approach provides opportunities for studying the emergent properties of atomic-scale mechanical and physicochemical interactions in a wide range of physical and biological networks

The Role of Nonlinear Dynamics in Quantitative Atomic Force Microscopy

Various methods of force measurement with the Atomic Force Microscope (AFM) are compared for their ability to accurately determine the tip-surface force from analysis of the nonlinear cantilever motion. It is explained how intermodulation, or the frequency mixing of multiple drive tones by the nonlinear tip-surface force, can be used to concentrate the nonlinear motion in a narrow band of frequency near the cantilevers fundamental resonance, where accuracy and sensitivity of force measurement are greatest. Two different methods for reconstructing tip-surface forces from intermodulation spectra are explained. The reconstruction of both conservative and dissipative tip-surface interactions from intermodulation spectra are demonstrated on simulated data.Comment: 25 pages (preprint, double space) 7 figure

Interaction imaging with amplitude-dependence force spectroscopy

Knowledge of surface forces is the key to understanding a large number of processes in fields ranging from physics to material science and biology. The most common method to study surfaces is dynamic atomic force microscopy (AFM). Dynamic AFM has been enormously successful in imaging surface topography, even to atomic resolution, but the force between the AFM tip and the surface remains unknown during imaging. Here, we present a new approach that combines high accuracy force measurements and high resolution scanning. The method, called amplitude-dependence force spectroscopy (ADFS) is based on the amplitude-dependence of the cantilever's response near resonance and allows for separate determination of both conservative and dissipative tip-surface interactions. We use ADFS to quantitatively study and map the nano-mechanical interaction between the AFM tip and heterogeneous polymer surfaces. ADFS is compatible with commercial atomic force microscopes and we anticipate its wide-spread use in taking AFM toward quantitative microscopy

Finite element modelling of atomic force microscope cantilever beams with uncertainty in material and dimensional parameters

Copyright © 2014 by Institute of Fundamental Technological Research Polish Academy of Sciences, Warsaw, PolandThe stiffness and the natural frequencies of a rectangular and a V-shaped micro-cantilever beams used in Atomic Force Microscope (AFM) were analysed using the Finite Element (FE) method. A determinate analysis in the material and dimensional parameters was first carried out to compare with published analytical and experimental results. Uncertainties in the beams’ parameters such as the material properties and dimensions due to the fabrication process were then modelled using a statistic FE analysis. It is found that for the rectangular micro-beam, a ±5% change in the value of the parameters could result in 3 to 8-folds (up to more than 45%) errors in the stiffness or the 1st natural frequency of the cantilever. Such big uncertainties need to be considered in the design and calibration of AFM to ensure the measurement accuracy at the micron and nano scales. In addition, a sensitivity analysis was carried out for the influence of the studied parameters. The finding provides useful guidelines on the design of micro-cantilevers used in the AFM technology.The research was supported by Sichuan International Research Collaboration Project (2014HH0022)

Applications of AFM in pharmaceutical sciences

Atomic force microscopy (AFM) is a high-resolution imaging technique that uses a small probe (tip and cantilever) to provide topographical information on surfaces in air or in liquid media. By pushing the tip into the surface or by pulling it away, nanomechanical data such as compliance (stiffness, Young’s Modulus) or adhesion, respectively, may be obtained and can also be presented visually in the form of maps displayed alongside topography images. This chapter outlines the principles of operation of AFM, describing some of the important imaging modes and then focuses on the use of the technique for pharmaceutical research. Areas include tablet coating and dissolution, crystal growth and polymorphism, particles and fibres, nanomedicine, nanotoxicology, drug-protein and protein-protein interactions, live cells, bacterial biofilms and viruses. Specific examples include mapping of ligand-receptor binding on cell surfaces, studies of protein-protein interactions to provide kinetic information and the potential of AFM to be used as an early diagnostic tool for cancer and other diseases. Many of these reported investigations are from 2011-2014, both from the literature and a few selected studies from the authors’ laboratories