Applications of atomic force microscopy-based imaging and force spectroscopy in assessing environmental interfacial processes

Rituximab, a monoclonal antibody against the CD20 molecule expressed on B cells, has revolutionized the treatment of B cell lymphomas. The use of rituximab significantly improves the long-term survival rates of lymphoma patients. However, there are still many patients who develop resistance to rituximab. Hence, the urgent need is enhancing the potency of anti-CD20 antibodies beyond that achieved with rituximab to provide effective therapies for more patients. Traditional studies about the killing mechanisms of rituximab are commonly based on optical microscopy, which cannot reveal the detailed situations due to the limit of 200-nm resolution. Quantitatively investigating the actions of rituximab at the nanoscale is still scarce. The advent of atomic force microscopy (AFM) provides a powerful and versatile platform for in situ investigating the nanoscale behaviors of individual live cells. The applications of AFM in life sciences in the past decade have yielded a lot of novel insights into cell biology and related diseases. In this article, the typical applications (e.g., ultra-microstructures, mechanical properties, and molecular recognition) of AFM in investigating the three killing mechanisms of rituximab at the nanoscale are summarized; the challenges facing AFM single-cell assay and its future directions are also discussed.

Background: The atomic force microscope (AFM) technique has proven to be a useful and versatile tool for the surface characterization of various materials. AFM is capable of providing three dimensional representations of surfaces down to the sub-nanometer scale resolution, with even atomic resolution. The aims of this mini review are to briefly illustrate our personal experience in AFM application for characterizing plasma-treated surface growth on different substrates, such as fluorocarbon (CFx) nano-structured films, polyethylene oxide (PEO) substrates and plasma deposited acrilic acid (pdAA) coatings, and nanocomposite materials, such as polydimethylsiloxane-gold (PDMS-Au) and chitosan-Au (CTO-Au), including the characterization of nanoparticle powder. Methods: The CFx films were obtained by plasma enhanced-chemical vapor deposition in the non-contact AFM mode and pdAA coatings by radiofrequency glow discharges fed with AA vapors and analyzed in the contact AFM mode. Coating morphology was analized by X-Ray photoelectron microscopy (XPS) and water contact angle (WCA). The AFM images of PDMS-Au and CTO-Au nanocomposites was also acquired and analyzed for their topography. Results: The surface topography, the root-mean square (RMS) surface roughness and the mean surface height of CFx coatings plasma-polymerised on polyethyleneterephthalate (PET) substrates were evaluated by AFM as a function of the deposition time, and AFM images obtained were used to gain detailed topographical information of the single nanostructure. By comparing the AFM images of pure PDMS with those of PDMS-Au it was possible to observe the topography of nanofillers embedded in a polymeric matrix or generated on a polymeric surface and also other main differences between the two materials. Conclusion: The AFM technique was shown to be a versatile and promising tool for the morphological characterization of growth of plasma-treated surfaces, such as CFx nano-structured films, PEO substrates and pdAA coatings, and for the topographical characterization of nanocomposite materials such as PDMs-Au and CTO-Au. Finally, AFM can be used as a simple method able to characterize the topography of as-received nanofillers, based on the attachment of the nanopowders on a bi-adhesive tape and on 3D image processing. Keywords: AFM, CFx nano-structured films, nanocomposite materials, nanofillers topography, plasma deposited acrylic acid coatings.

Given the social demand for self-powering wearable electronics, it is necessary to develop composite materials that exhibit both good flexibility and excellent piezoelectric performances. Intensive research on synthesis methods and devising characterization techniques for piezoelectric nanomaterials in various forms has been conducted. In particular, characterization techniques for piezoelectric nanomaterials require different approaches from those for conventional bulk materials. Atomic force microscopy (AFM)-based characterization techniques work based on the local physical interactions between the AFM tip and sample surfaces, making them an irreplaceable tool for studying the electromechanical properties of piezoelectric nanomaterials. Piezoresponse force microscopy (PFM), conductive AFM (C-AFM), and lateral force microscopy (LFM) are three representative AFM-based techniques used to characterize the piezoelectric and ferroelectric properties of nanomaterials. Coupled with the appearance of diverse novel nanomaterials such nanowires, free-standing nanorods, and electrospun nanofibers, AFM-based characterization techniques are becoming freer from artifacts and the need for quantitative measurements. PFM was initially developed to image the microstructures of piezoelectric materials, and well-calibrated techniques designed to realize quantitative measurements have been applied to nanomaterials. In contrast, C-AFM and LFM were initially used to measure the conductivity of diverse materials and the nanotribology of material surfaces. Over the last decade, they have proved their versatility and can now be used to evaluate the direct piezoelectric effect and the mechanical properties of piezoelectric nanomaterials. In these cases, systematic understanding with regard to the measurement principles is required for accurate measurements and analyses. In the present review article, we discuss earlier work in which AFM-based electromechanical characterization techniques were applied to nanomaterials to evaluate piezoelectric and ferroelectric properties. Also discussed is the importance of gaining a comprehensive understanding of the resulting signals.

As a cantilever structure, atomic force microscope (AFM) can be either modeled as a beam, plate or a simple one degree-of-freedom (DOF) system depending on its geometry and application scenario. The AFM structure can experience the deformation shapes of vertical bending, lateral bending, torsion, extension and couplings between these four deformations depending on the excitation mode. As a small structure of micron scale, forces like van der Waals (vdW) force, surface stress, electrostatic force and residual stress can have significant influence on the AFM deflection. When the AFM tip is in contact with the sample surface, different contact mechanics models are needed depending on the tip geometry, AFM operating mode and tip, sample surface material properties. In dynamic mode, the AFM tip–sample surface intermittent contact is a complicated nonlinear dynamics problem. As a powerful tool, the AFM application is already beyond the stage of being used to image the sample surface topography. Nowadays, AFM is used more often to extract the sample materials properties such as Young’s modulus, surface energy/adhesion and viscosity. How to properly model the AFM structure with different deformations and their coupling under different forces and the tip–sample surface interaction is vital to linking the experimentally measured data correctly with the sample surface material properties. This chapter reviews the different models concerning the AFM structure (static) deformations, external residual forces modeling, tip–surface contact and the AFM dynamics. This chapter is intended to provide a comprehensive review rather than an in-depth discussion on those models. Because there are too many factors influencing the experimentally measured data during the application of AFM, it is extremely difficult to consider all these factors in one model for AFM if not impossible. Because there are too many factors influencing the AFM deformations/dynamics, it will be extremely difficult if not impossible to link all of the influencing factors to the experimental data. Therefore, in the modeling aspect, certain assumptions must be made to render the problem solvable. One of the major purposes of this chapter is to discuss and analyze the assumptions of those models and by doing so we try to outline the applicability ranges of those models. At the same time by analyzing the assumptions of the models applied to the AFM, the limitations of some models are also presented. Pointing out the limitations of those models which work fine with certain application scenarios is intended to make the applicability ranges of the models clearer and also helps to better interpret the experimental data. Only the dominant factors should be considered in a model and the other factors must be neglected to have a workable model. However, for different AFM applications the dominant factors are varied and thus transferring the model developed for one AFM application to another one can be inappropriate or even wrong. The analysis on the model assumption thus plays an important role of applying one model developed for certain application scenario to other applications.

Open the door to the atomic world by single-molecule atomic force microscopy

Temporal sequence of the human RBCs' vesiculation observed in nano-scale with application of AFM and complementary techniques

Research progress in quantifying the mechanical properties of single living cells using atomic force microscopy

Nanoemulsion-based systems are widely applied in food industries for protecting active ingredients against oxidation and degradation and controlling the release rate of active core ingredients under particular conditions. Visualizing the interface morphology and measuring the interfacial interaction forces of nanoemulsion droplets are essential to tailor and design intelligent nanoemulsion-based systems. Atomic force microscopy (AFM) is being established as an important technique for interface characterization, due to its unique advantages over traditional imaging and surface force-determining approaches. However, there is a gap in knowledge about the applicability of AFM in characterizing the droplet interface properties of nanoemulsions. This review aims to describe the fundamentals of the AFM technique and nanoemulsions, mainly focusing on the recent use of AFM to investigate nanoemulsion properties. In addition, by reviewing interfacial studies on emulsions in general, perspectives for the further development of AFM to study nanoemulsions are also discussed.

Carbon nanotubes (CNTs) are known to enhance the scanning performance of AFM tips when mounted on AFM tips. There are different ways to synthesize CNTs, i.e. arc-discharge and chemical vapor deposition (CVD). CNTs have been directly grown on atomic force microscopy (AFM) tips by CVD. CNTs produced by arc-discharge method have been mechanically attached onto AFM tips to compare the performance of different types of CNTs. AFM images have been gathered with these CNT AFM tips. Present results show that arc-discharge CNT AFM tips have better scanning performances than the Si AFM tips.

Biological atomic force microscopy (also known as scanning force microscopy) has advanced in many areas. Some of the new applications of atomic force microscopy to DNA and protein research are outlined. Advances have occurred in both imaging and nonimaging uses of atomic force microscopy. Advances in atomic force microscopy imaging have been seen both in the imaging of immobile samples and in the imaging of motion and processes. Advances in nonimaging atomic force microscopy include the use of force curves to measure intermolecular forces, force mapping, and measurements of protein motion.

Nanointerrogation of ultrasonic contrast agent microbubbles using atomic force microscopy

The Achilles tendon consists mainly of type I collagen fibers that contain collagen fibrils. When the Achilles tendon is injured, it is inflamed. The collagenase-induced model has been widely used to study tendinitis. The major advantages of atomic force microscopy (AFM) over conventional optical and electron microscopy for bio-imaging include its non-requirement of a special coating and vacuum, and its capability to perform imaging in all environments. AFM force-distance measurements have become a fundamental tool in the fields of surface chemistry, biochemistry and materials science. Therefore, the changes in the ultrastructure and adhesion force of the collagen fibrils on the Achilles tendons of rats with Achilles tendinitis were observed using AFM. The changes in the structure of the Achilles tendons were evaluated based on the diameter and D-banding of the collagen fibrils. Collagenase-induced Achilles tendinitis was induced with the injection of 30 microl crude collagenase into 7-week-old male Sprague-Dawley rats. The animals were each sacrificed on the first, second, third, fifth and seventh day after the collagenase injection. The normal and injured Achilles tendons were fixed in 4% buffered formalin and dehydrated with increasing concentrations of ethanol. AFM was performed using the non-contact mode at the resolution of 512 x 512 pixels, with a scan speed of 0.8 line/sec. The adhesion force was measured via the force-distance curve that resulted from the interactions between the AFM tip and the collagen fibril sample using the contact mode. The diameter of the collagen fibrils in the Achilles tendons significantly decreased (p < 0.05) after the collagenase injection, and the pattern of the D-banding of the collagen fibrils was similar to that of the diameter changes. The adhesion force decreased until the fifth day after the collagenase injection, but increased on the seventh day after the collagenase injection (p < 0.0001).

In AFM measurements of surface morphology, the locality is a traditional assumption, i.e., the load recorded by AFM is simply the function of the distance between the tip of AFM and the point on a sample right opposite the tip [Giessibl, F. J., 2003, “Advances in Atomic Force Microscopy,” Rev. Mod. Phys., 75, pp. 949–983]. This paper presents that nonlocality effect may play an important role in atomic force microscopic (AFM) measurement. The nonlocality of AFM measurement results from two different finite scales: the finite scale of the characteristic intermolecular interaction distance and the geometric size of AFM tip. With a coupled molecular-continuum method, we analyzed this nonlocality effect in detail. It is found that the nonlocality effect can be formulated by a few dimensionless parameters characterizing the ratio of the following scales: the characteristic intermolecular interaction distance between the AFM tip and the sample, the characteristic size of the tip and the characteristic nano-structure and∕or the nanoscale roughness on the surface of a sample. The present work also suggests a data processing algorithm—the approaching method, which can reduce the nonlocality effect in AFM measurement of surface morphology effectively.

An attempt was made to electrodeposit copper on a nanosize atomic force microscopy (AFM) tip by varying the magnitude of current densities with plating time and vice versa. Changes in the current density and plating time resulted in significant changes in the morphology of copper deposits on the AFM probe containing the tip. Scanning electron microscopy (SEM) results revealed that a nonuniform layer of copper was formed on the open areas surrounding the tip; however, no copper deposition was observed on the AFM tip in the absence of photoresist poly(methyl methacrylate) (PMMA). The electron-beam lithography technique proved to be a versatile tool for the electrodeposition of copper on the AFM tip in the presence of photoresist PMMA. Copper was electrochemically deposited on the e-beam modified regions of the AFM probe at a current density of with plating times ranging from 300 to 2400 s.

Water bridge dynamics between an atomic force microscopy (AFM) tip and a flat substrate is studied by using a multibody dissipative particle dynamics (MDPD) model. First, the numerical model is validated by comparing the present results of droplet contact angles and liquid bridges with those reported in the literature. Then, the ability of MDPD to capture the meniscus shape and behavior for different operating conditions and geometric parameters is examined for both static and dynamic cases. Hence, several parametric studies and analyses of the AFM tip configuration and its operating conditions are reported. It is found that a critical capillary number of about 0.001 is calculated based on 5% change on the force measurements between the static and dynamic results. It is also demonstrated that the hysteresis behavior in the capillary force exerted on the AFM tip can be successfully predicted by using the MDPD model when the tip approaches or retracts from the substrate. Moreover, there is an excellent agreement in the results of breakup distance for different water bridge volumes between the predictions of the MDPD model and the theory. Also, the hysteresis of capillary force exerted on an AFM tip composed of multibody design is studied. The prediction on the transition of the capillary force vs distance between the AFM tip and the substrate is in good agreement with the experimental results. Therefore, we demonstrate a validated MDPD model which can successfully capture liquid bridge dynamics. This model can be used as a powerful design tool for meniscus manipulation technology, such as dip-pen nanolithography, as well as for studying dynamic, e.g., tapping mode AFM tip, interactions with a liquid bridge.