Application Of Atomic Force Microscopy Research Articles

Application of Atomic Force Microscopy as Advanced Asphalt Testing Technology: A Comprehensive Review.

In the past three decades, researchers have engaged in the relationship between the composition, macro performance, and microstructure of asphalt. There are many research results in the use of atomic force microscopy (AFM) to study the microstructure and related mechanisms of asphalt. Based on previous studies, the performance of asphalt from its microstructure has been observed and analyzed, and different evaluation indices and modification methods have been proposed, providing guidance toward improving the performance of asphalt materials and benefiting potential applications. This review focuses on the typical application and analysis of AFM in the study of the aging regeneration and modification properties of asphalt. Additionally, this review introduces the history of the rheological and chemical testing of asphalt materials and the history of using AFM to investigate asphalt. Furthermore, this review introduces the basic principles of various modes of application of AFM in the microstructure of asphalt, providing a research direction for the further popularization and application of AFM in asphalt or other materials in the future. This review aims to provide a reference and direction for researchers to further popularize the application of AFM in asphalt and standardize the testing methods of AFM. This paper is also helpful in further exploring the relationship between the microstructure and macro performance of asphalt.

Atomic force microscopy in energetic materials research: A review

Modern trends in the development of energetic materials include the various methods of particle surface modification and the widespread use of nanosized powders. Atomic force microscopy (AFM) is a useful, but often overlooked advanced tool for the investigation of surface, subsurface, and interface properties of energetic compounds. This review highlights the diverse applications of AFM, and provides the various methods of AFM to investigate energetic materials, along with sample preparation techniques. We show that AFM has not only the value for imaging the surface, but also the capability to manipulate and perform the real experiments at the nanoscale. It could be a mechanical stimulation of the crystal and observation of the surface changes after it, or the attachment of the energetic crystal to the tipless cantilever, which approaches the polymeric sample to derive the adhesion force between two materials. We anticipate that over time the AFM-based techniques will be used more and more actively in the research of energetic materials and will benefit our better understanding of the processes taking place at interfaces and surfaces of energetic compounds.

Extending applications of AFM to fluidic AFM in single living cell studies.

In this article, a review of a series of applications of atomic force microscopy (AFM) and fluidic Atomic Force Microscopy (fluidic AFM, hereafter fluidFM) in single-cell studies is presented. AFM applications involving single-cell and extracellular vesicle (EV) studies, colloidal force spectroscopy, and single-cell adhesion measurements are discussed. FluidFM is an offshoot of AFM that combines a microfluidic cantilever with AFM and has enabled the research community to conduct biological, pathological, and pharmacological studies on cells at the single-cell level in a liquid environment. In this review, capacities of fluidFM are discussed to illustrate (1) the speed with which sequential measurements of adhesion using coated colloid beads can be done, (2) the ability to assess lateral binding forces of endothelial or epithelial cells in a confluent cell monolayer in an appropriate physiological environment, and (3) the ease of measurement of vertical binding forces of intercellular adhesion between heterogeneous cells. Furthermore, key applications of fluidFM are reviewed regarding to EV absorption, manipulation of a single living cell by intracellular injection, sampling of cellular fluid from a single living cell, patch clamping, and mass measurements of a single living cell.

Gas cluster etching for the universal preparation of polymer composites for nano chemical and mechanical analysis with AFM

Atomic force microscopy (AFM) based techniques that probe nanomechanical and nanochemical features are valuable tools for studying composite surfaces at high-resolution. However, the application of AFM, particularly at resolutions less than 50 nm per pixel, is limited to sample surfaces that are smooth relative to the tip dimensions and damage-free. As a result, high-resolution AFM is limited in technologically relevant polymer composite systems where current sample preparation techniques can fail to produce the necessary pristine surfaces. Here, we apply gas cluster ion beam (GCIB) etching to prepare composite materials for nanomechanical and nanochemical analysis. We demonstrate that the GCIB can effectively remove material and produce damage free surfaces for composites comprised of PMMA or PS confined in the 7 nm diameter pores of an organosilicate matrix. AFM-IR measurements on the etched region indicate a high degree of hydrogen bonding between the carbonyl groups of the confined PMMA and the hydroxyl groups on the pore walls, while maps of loss tangent can identify the 7 nm polymer domains within the organosilicate matrix. This work demonstrates that GCIB is an effective tool for nanocomposite surface preparation and could enable a new range of materials to be studied with AFM at high resolution.

Atomic Force Microscopy Application for the Measurement of Infliximab Concentration in Healthy Donors and Pediatric Patients with Inflammatory Bowel Disease.

The use of infliximab has completely changed the therapeutic landscape in inflammatory bowel disease. However, despite its proven efficacy to induce and maintain clinical remission, increasing evidence suggests that treatment failure may be associated with inadequate drug blood concentrations. The introduction of biosensors based on different nanostructured materials for the rapid quantification of drugs has been proposed for therapeutic drug monitoring. This study aimed to apply atomic force microscopy (AFM)-based nanoassay for the measurement of infliximab concentration in serum samples of healthy donors and pediatric IBD patients. This assay measured the height signal variation of a nanostructured gold surface covered with a self-assembled monolayer of alkanethiols. Inside this monolayer, we embedded the DNA conjugated with a tumor necrosis factor able to recognize the drug. The system was initially fine-tuned by testing known infliximab concentrations (0, 20, 30, 40, and 50 nM) in buffer and then spiking the same concentrations of infliximab into the sera of healthy donors, followed by testing pediatric IBD patients. A good correlation between height variation and drug concentration was found in the buffer in both healthy donors and pediatric IBD patients (p-value < 0.05), demonstrating the promising use of AFM nanoassay in TDM.

Machine learning to probe modal interaction in dynamic atomic force microscopy

Modal interactions are pervasive effects that commonly emerge in nanomechanical systems. The coupling of vibrating modes can be leveraged in many ways, including to enhance sensing or to disclose complex phenomenologies. In this work we show how machine learning and data-driven approaches could be used to capture intermodal coupling. We employ a quasi-recurrent neural network (QRNN) for identifying mode coupling and verify its applicability on experimental data obtained from tapping mode atomic force microscopy (AFM). Hidden units of the QRNN are monitored to trace fingerprints of modes activation and to quantify their contributions over the global distortion of orbits in the phase space. To demonstrate the broad applicability of the method, the trained model is re-applied over different experiments and on diverse materials. Over a range of tip-sample configurations, dynamic AFM possesses features general enough to be seized by the QRNN and it is not required an ad-hoc re-training for the identification of interacting modes. Our study opens up a route for utilizing established machine learning techniques for rapid recognition of nonlinear complex effect such as internal resonances in nanotechnology. The QRNN analysis is meant to assist AFM sensing operations when exploiting modal interaction to enhance the signal-to-noise ratio of higher harmonics and provide high resolution compositional contrast in multi-frequency AFM applications.

Recent Trends in AFM Imaging Speed and Improvement Methods

: Atomic force microscope (AFM) has become the main tool for observation and manipulation in nanotechnology research due to its nano-meter high resolution, but the slow imaging speed is one of the important reasons hindering the further development of AFM. This article first introduces the applications of AFM in cell biology in recent years, expresses the importance of rapid imaging in cell biology, and then summarizes the reasons affecting the imaging speed of AFM from three aspects: the limited bandwidth of system mechanical components, obvious inherent characteristics of piezoelectric scanners, and complex image processing algorithms. The improvement and optimization methods of mechanical parts or structure, control algorithm and image processing are reviewed for different influence reasons. Then, the advantages and of different improvement methods, as well as the improved imaging speed and imaging quality improvement effects, are compared. Imaging speed and resolution are both several to dozens of times higher than before, while ensuring image quality and without damaging the samples. The aim of this review is to enable students, the public and even experts of different knowledge backgrounds to learn directly, and select realizable improvement methods according to realistic conditions. Finally, the future development trend and further prospects of high-speed AFM are discussed.

Very-high-frequency probes for atomic force microscopy with silicon optomechanics

Atomic force microscopy (AFM) has been consistently supporting nanosciences and nanotechnologies for over 30 years and is used in many fields from condensed matter physics to biology. It enables the measurement of very weak forces at the nanoscale, thus elucidating the interactions at play in fundamental processes. Here, we leverage the combined benefits of micro/nanoelectromechanical systems and cavity optomechanics to fabricate a sensor for dynamic mode AFM at a frequency above 100 MHz. This frequency is two decades above the fastest commercial AFM probes, suggesting an opportunity for measuring forces at timescales unexplored thus far. The fabrication is achieved using very-large-scale integration technologies derived from photonic silicon circuits. The probe’s optomechanical ring cavity is coupled to a 1.55 μm laser light and features a 130 MHz mechanical resonance mode with a quality factor of 900 in air. A limit of detection in the displacement of 3 × 10−16 m/√Hz is obtained, enabling the detection of the Brownian motion of the probe and paving the way for force sensing experiments in the dynamic mode with a working vibration amplitude in the picometer range. When inserted in a custom AFM instrument embodiment, this optomechanical sensor demonstrates the capacity to perform force-distance measurements and to maintain a constant interaction strength between the tip and sample, an essential requirement for AFM applications. Experiments indeed show a stable closed-loop operation with a setpoint of 4 nN/nm for an unprecedented subpicometer vibration amplitude, where the tip–sample interaction is mediated by a stretched water meniscus.

Force Sensing on Cells and Tissues by Atomic Force Microscopy.

Biosensors are aimed at detecting tiny physical and chemical stimuli in biological systems. Physical forces are ubiquitous, being implied in all cellular processes, including cell adhesion, migration, and differentiation. Given the strong interplay between cells and their microenvironment, the extracellular matrix (ECM) and the structural and mechanical properties of the ECM play an important role in the transmission of external stimuli to single cells within the tissue. Vice versa, cells themselves also use self-generated forces to probe the biophysical properties of the ECM. ECM mechanics influence cell fate, regulate tissue development, and show peculiar features in health and disease conditions of living organisms. Force sensing in biological systems is therefore crucial to dissecting and understanding complex biological processes, such as mechanotransduction. Atomic Force Microscopy (AFM), which can both sense and apply forces at the nanoscale, with sub-nanonewton sensitivity, represents an enabling technology and a crucial experimental tool in biophysics and mechanobiology. In this work, we report on the application of AFM to the study of biomechanical fingerprints of different components of biological systems, such as the ECM, the whole cell, and cellular components, such as the nucleus, lamellipodia and the glycocalyx. We show that physical observables such as the (spatially resolved) Young’s Modulus (YM) of elasticity of ECMs or cells, and the effective thickness and stiffness of the glycocalyx, can be quantitatively characterized by AFM. Their modification can be correlated to changes in the microenvironment, physio-pathological conditions, or gene regulation.

Characterization of bituminite in Kimmeridge Clay by confocal laser scanning and atomic force microscopy

This work investigates bituminite (amorphous sedimentary organic matter) in Upper Jurassic Kimmeridge Clay source rock via confocal laser scanning microscopy (CLSM) and atomic force microscopy (AFM). These petrographic tools were used to provide better understanding of the nature of bituminite, which has been historically difficult to identify and differentiate from similar organic matter types in source rocks. As part of an International Committee for Coal and Organic Petrology (ICCP) working group, an immature (0.42% vitrinite reflectance), organic-rich (44.1 wt% total organic carbon content) sample of Kimmeridge Clay was distributed to multiple laboratories for CLSM characterization. The primary observations from CLSM imaging and spectroscopy include: 1) the interpreted presence of Botryococcus algae as a contributor to bituminite precursors; 2) color red-shift of sulfide reflectance and bituminite auto-fluorescence from below the sample surface; 3) positive alteration of bituminite from laser-induced photo-oxidation of the sample surface, including fluorescence blue-shift; 4) fluorescence blue-shift associated to higher fluorescence intensity regions in bituminite indicative of compositional (fluorophore) differences; 5) the need for fluorescence spectroscopy standardization as applied via CLSM; and 6) the suitability of CLSM fluorescence spectroscopy to predict solid bitumen reflectance from bituminite spectral emission via calibration to an extant dataset. Secondary CLSM observations include detection of reflected laser light from highly reflective inclusions in bituminite, including sulfides and fusinite, and radiolytic alteration of bituminite caused by substitution of U for Fe in sulfides. Findings from AFM include the observation that surface roughening or surface flattening of bituminite are induced by differential broad ion beam (BIB) milling and are dependent on the location and scale of AFM topology measurement. This result highlights our still limited understanding of the effects of BIB milling on sedimentary organic matter and indicates the need for further research before this technique can be advanced as a standard practice in petrographic sample preparation. Collectively, the results of this study illustrate the general applicability and versatility of AFM and CLSM as tools for organic petrology research, specifically for better understanding of the nature and properties of the bituminite maceral.

Atomic Force Microscopy for Structural and Biophysical Investigations on Nuclear Pore Complexes.

Atomic force microscopy (AFM) enables simultaneous generation of topographical and biophysical maps of surfaces of biological samples at nanoresolution in physiologically relevant environments. Here, we describe the application of AFM to study nuclear pore complexes from structural and biophysical aspects.

Atomic Force Microscopy of DNA and DNA-Protein Interactions.

Atomic force microscopy (AFM) is a microscopy technique that uses a sharp probe to trace a sample surface at nanometer resolution. For biological applications, one of its key advantages is its ability to visualize the substructure of single molecules and molecular complexes in an aqueous environment. Here, we describe the application of AFM to determine the secondary and tertiary structure of surface-bound DNA, and its interactions with proteins.

In Operando Atomic Force Microscopy Imaging of Electrochemical Interfaces: A Short Perspective

Electrochemical interfaces are at the core of many important current applications, from corrosion and biophysics to electrocatalytic and battery interfaces. Further understanding in the processes taking place at these interfaces is often linked to better observation techniques. In situ or in operando imaging and characterization of the electrochemical interface helps improve our understanding of structural sequences and kinetics of complex processes. Atomic force microscopy (AFM) offers a unique combination to monitor surface morphology and mechanical properties at micro‐ and nanoscale surfaces and solid–electrolyte interfaces. Two examples are given where the application of AFM during electrochemical processes is clearly useful. Organic inhibitors and their behavior play an important role in corrosion mitigation and the influence of thiol monolayers on dealloying is reported: Zinc films find application for coatings or Zn batteries and an in situ electrodeposition study is shortly described. With the ongoing improvement of computational simulations, the broadening of spatiotemporal scales possible with AFM imaging and its combination with mechanical information points in a prospective future for in operando AFM.

Advances in Atomic Force Microscopy: Imaging of Two- and Three-Dimensional Interfacial Water.

Interfacial water is closely related to many core scientific and technological issues, covering a broad range of fields, such as material science, geochemistry, electrochemistry and biology. The understanding of the structure and dynamics of interfacial water is the basis of dealing with a series of issues in science and technology. In recent years, atomic force microscopy (AFM) with ultrahigh resolution has become a very powerful option for the understanding of the complex structural and dynamic properties of interfacial water on solid surfaces. In this perspective, we provide an overview of the application of AFM in the study of two dimensional (2D) or three dimensional (3D) interfacial water, and present the prospect and challenges of the AFM-related techniques in experiments and simulations, in order to gain a better understanding of the physicochemical properties of interfacial water.

Enhancing higher-order eigenmodes of AFM using bridge/cantilever coupled system

The wide application of multi-frequency atomic force microscopy (AFM) places higher demands on the higher-order modes response of the cantilever. The response of the higher modes however is generally weaker than that of the fundamental mode in air. Researchers have proposed many methods, most of which involve cantilever modification, to enhance higher-order eigenmodes response. These previous results are proved to be effective, but the microfabrication is expensive. In this article, we propose a novel model based on bridge/cantilever coupled system to enhance the higher-order modes response of AFM cantilever. The segmented beam model provides a new thinking to explain the appearance of undesired peaks in mode analysis of cantilever. Through theoretical analysis and simulation, we find that higher resonance modes are enhanced by tuning the bridge to match the high resonances of the single clamped cantilever. The length, thickness of the coupled system and the location of excitation can affect the enhancement. In summary, this model provides a new way to improve higher mode response for multi-frequency and other high bandwidth applications of AFM.

Research Techniques Made Simple: Analysis of Skin Cell and Tissue Mechanics Using Atomic Force Microscopy

Atomic force microscopy (AFM) is a powerful technique for nanoscale imaging and mechanical analysis of biological specimens. It is based on the highly sensitive detection of forces and displacement of a sharp-tipped cantilever as it scans the surface of an object. Because it requires minimal sample processing and preparation, AFM is particularly advantageous for the analysis of cells and tissues in their near-native state. Moreover, recent advances in Bio-AFM systems and the combination with light microscopy imaging have greatly enhanced the application of AFM in biological research. In the field of dermatology, the method has led to important insights into our understanding of the biomechanics of normal healthy skin and the pathogenesis of a variety of skin diseases. In this Research Techniques Made Simple article, we review the fundamental principles of AFM, how AFM can be applied to the analysis of cell and tissue mechanics, and recent applications of AFM in skin science and dermatology.

Application of AFM, TEM, and NTA for characterization of exosomes produced by placenta-derived mesenchymal cells

Exosomes and microvesicles usually require characterization at the single-particle level. The most commonly used methods for this purpose are transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). However, atomic force microscopy (AFM) is also a promising method for the characterization of exosomes, and its opportunities seem underestimated. Here we describe the characterization of exosomes isolated from the conditioned media of human placenta cells using AFM, TEM, and NTA; we focus on the technical aspects of AFM imaging and data processing.

Path planning in three dimensional live environment with randomly moving obstacles for viscoelastic bio-particle.

Significant capabilities of atomic force microscopy (AFM) such as operating in various environments and scales made it a useful device in different operations. According to AFM abilities and applications, in this work, the path through the live environment with fixed and moving obstacles that are distributed all over the space randomly has been provided. The optimized path has been discovered in this article based on the applications mentioned above. Since for biological applications, the tool's accuracy plays an important role in success and reliability of the operation, in this article, the cost function is defined as combination of the tool's error, the maximum applied force on the tool, and the maximum deformation of the particle to be minimized. In this regard, constraints which limit the particle's motion and speed such as critical force and time and the maximum applied force have been considered. While in living environment obstacle existence is possible, fixed and moving obstacles with random profile and distribution will be considered. Routing of viscoelastic particle considering above conditions has been performed and comparison with the previous works proved the correctness of the path. The effects of different constraints have been compared using path optimization in different situations. The time of path planning for critical force and time was about 117.657, for the maximum applied force 118.240, and for all constraints together was 120.540 s which shows that the applied force constraint has been more effective than others and increases path planning time.

AFM-Based Correlative Microscopy Illuminates Human Pathogens.

Microbes have an arsenal of virulence factors that contribute to their pathogenicity. A number of challenges remain to fully understand disease transmission, fitness landscape, antimicrobial resistance and host heterogeneity. A variety of tools have been used to address diverse aspects of pathogenicity, from molecular host-pathogen interactions to the mechanisms of disease acquisition and transmission. Current gaps in our knowledge include a more direct understanding of host-pathogen interactions, including signaling at interfaces, and direct phenotypic confirmation of pathogenicity. Correlative microscopy has been gaining traction to address the many challenges currently faced in biomedicine, in particular the combination of optical and atomic force microscopy (AFM). AFM, generates high-resolution surface topographical images, and quantifies mechanical properties at the pN scale under physiologically relevant conditions. When combined with optical microscopy, AFM probes pathogen surfaces and their physical and molecular interaction with host cells, while the various modes of optical microscopy view internal cellular responses of the pathogen and host. Here we review the most recent advances in our understanding of pathogens, recent applications of AFM to the field, how correlative AFM-optical microspectroscopy and microscopy have been used to illuminate pathogenicity and how these methods can reach their full potential for studying host-pathogen interactions.

Atomic Force Microscopy for Live-Cell and Hydrogel Measurement.

Atomic force microscopy (AFM) has emerged as a popular method for determining the mechanical properties of cells, their components, and biomaterials. Here, we describe AFM setup and application to obtain stiffness measurements from single indentations for hydrogels and myofibroblasts.