Spiral scanning method for atomic force microscopy

A spiral scanning method is proposed for atomic force microscopy with thoroughgoing analysis and implementation. Comparing with the traditional line-by-line scanning method, the spiral scanning method demonstrates higher imaging speed, minor image distortion, and lower acceleration, which can damage the piezoelectric scanner. Employing the spiral scanning method to replace the line-by-line scanning method, the experiment shows that the time to complete an imaging cycle can be reduced from 800 s to 314 s without sacrificing the image resolution.     

Nanofabrication with atomic force microscopy

Atomic force microscopy (AFM) was developed in 1986. It is an important and versatile surface technique, and is used in many research fields. In this review, we have summarized the methods and applications of AFM, with emphasis on nanofabrication. AFM is capable of visualizing surface properties at high spatial resolution and determining biomolecular interaction as well as fabricating nanostructures. Recently, AFM-based nanotechnologies such as nanomanipulation, force lithography, nanografting, nanooxidation and dip-pen nanolithography were developed rapidly. AFM tip (typical radius ranged from several nanometers to tens of nanometers) is used to modify the sample surface, either physically or chemically, at nanometer scale. Nanopatterns composed of semiconductors, metal, biomolecules, polymers, etc., were constructed with various AFM-based nanotechnologies, thus making AFM a promising technique for nanofabrication. AFM-based nanotechnologies have potential applications in nanoelectronics, bioanalysis, biosensors, actuators and high-density data storage devices.     

Advances in atomic force microscopy for single-cell analysis

Single-cell analysis has been considered as a promising way to uncover the underlying mechanisms guiding the mysteries of life activities, which considerably complements traditional ensemble assays and yields novel insights into cell biology. The advent of atomic force microscopy (AFM) provides a potent tool for investigating the structures and properties of native biological samples at the micro/nanoscale under near-physiological conditions, which promotes the studies of single-cell behaviors. In the past decades, AFM has achieved great success in single-cell observation and manipulation for biomedical applications, demonstrating the excellent capabilities of AFM in addressing biological issues at the single-cell level with unprecedented spatiotemporal resolution. In this article, we review the recent advances in single-cell analysis that has been made with the utilization of AFM, and provide perspectives for future progression.

     

Chaos in dynamic atomic force microscopy

In tapping mode atomic force microscopy (AFM) the highly nonlinear tip-sample interaction gives rise to a complicated dynamics of the microcantilever. Apart from the well-known bistability under typical imaging conditions the system exhibits a complex dynamics at small average tip-sample distances, which are typical operation conditions for mechanical dynamic nanomanipulation. In order to investigate the dynamics at small average tip sample gaps experimental time series data are analysed employing nonlinear analysis tools and spectral analysis. The correlation dimension is computed together with a bifurcation diagram. By using statistical correlation measures such as the Kullback-Leibler distance, cross-correlation and mutual information the dataset can be segmented into different regimes. The analysis reveals period-3, period-2 and period-4 behaviour, as well as a weakly chaotic regime.     

Microfluidic bacterial traps for simultaneous fluorescence and atomic force microscopy

The atomic force microscope has become an established research tool for imaging microorganisms with unprecedented resolution.However,its use in microbiology has been limited by the difficulty of proper bacterial immobilization.Here,we have developed a microfluidic device that solves the issue of bacterial immobilization for atomic force microscopy under physiological conditions.Our device is able to rapidly immobilize bacteria in well-defined positions and subsequently release the cells for quick sample exchange.The developed device also allows simultaneous fluorescence analysis to assess the bacterial viability during atomic force microscope imaging.We demonstrated the potential of our approach for the immobilization of rod-shaped Escherichia coli and Bacillus subtilis.Using our device,we observed buffer-dependent morphological changes of the bacterial envelope mediated by the antimicrobial peptide CM15.Our approach to bacterial immobilization makes sample preparation much simpler and more reliable,thereby accelerating atomic force microscopy studies at the single-cell level.     

Measurement of interfiber friction force for pulp fibers by atomic force microscopy

Interfiber friction in paper exists in fiber suspensions, fiber flocs, and fiber networks. The interfiber friction force is, therefore, important both in papermaking and in the use of paper. The objective of this research is to develop a methodology using atomic force microscopy (AFM) for the direct measurement of the friction force between pulp fibers. Different factors such as AFM scanning velocity, contact area, and fiber surface roughness were investigated. The results show that AFM is an effective tool for measuring micro-scale interfiber friction forces. Both AFM scanning velocity and fiber surface roughness affect the measured results. The coefficient of friction increases, but the initial adhesion force decreases, with increasing fiber surface roughness.     

Single-molecule switching with non-contact atomic force microscopy

We report upon controlled switching of a single 3,4,9,10-perylene tetracarboxylic diimide derivative molecule on a rutile TiO(2)(110) surface using a non-contact atomic force microscope at room temperature. After submonolayer deposition, the molecules adsorb tilted on the bridging oxygen row. Individual molecules can be manipulated by the atomic force microscope tip in a well-controlled manner. The molecules are switched from one side of the row to the other using a simple approach, taking benefit of the sample tilt and the topography of the titania substrate. From density functional theory investigations we obtain the adsorption energies of different positions of the molecule. These adsorption energies are in very good agreement with our experimental observations.     

High-speed atomic force microscopy coming of age

High-speed atomic force microscopy (HS-AFM) is now materialized. It allows direct visualization of dynamic structural changes and dynamic processes of functioning biological molecules in physiological solutions, at high spatiotemporal resolution. Dynamic molecular events unselectively appear in detail in an AFM movie, facilitating our understanding of how biological molecules operate to function. This review describes a historical overview of technical development towards HS-AFM, summarizes elementary devices and techniques used in the current HS-AFM, and then highlights recent imaging studies. Finally, future challenges of HS-AFM studies are briefly discussed.     

Contact atomic force microscopy of biological tissues

The forces of adhesion of the normal and tumor cells of the human stomach epithelium to the probe of an atomic force microscope have been measured for the first time. It is established that the adhesion and contact stiffness of malignant cells are significantly lower than those of the normal cells.     

Multimodal atomic force microscopy: Biological imaging using atomic force microscopy combined with light fluorescence and confocal microscopies and electrophysiologic recording

Because the atomic force microscope (AFM) allows molecular resolution imaging of hydrated specimens, it provides a unique window to the microscopic biological world. A high signal-to-noise ratio in AFM images sets them apart from the images obtained from other techniques: One does not need extensive image analyses often required by other techniques to obtain high-resolution information. AFM can provide molecular details on crystalline as well as amorphous materials. However, it is often limited in providing identity of the imaged structures, especially in a complex system such as a cellular membrane. AFM's application for biological imaging will rely on an unambiguous identification of imaged structures. For mixed macromolecules, it may be essential to make critical comparisons of the same structural features imaged with AFM and other techniques such as light fluorescence and confocal microscopies, electron microscopy and X-ray diffraction, and biochemical, immunologic, and pharmacologic techniques and electrophysiologic recordings. Significantly, the simple design of AFM allows it to be integrated with other techniques for simultaneous multimodal imaging. Recent combined multimodal imaging include light fluorescence, confocal, and near-field optical imaging as well as electrophysiologic recordings. Preliminary studies from such multimodal imaging include 1) an independent identification of macromolecules in a complex specimen using appropriately labeled markers such as fluorescent-dye labeled antibodies or dark-field microscopy; 2) imaging real-time reorganization of surface features using laser confocal and AFM; 3) a direct correlation of structural features and ion transfer via pores in a membrane; and 4) macromolecular complexes such as receptor-ligand and antigen-antibody. These features of a multimodal imaging system will provide new and significant avenues for a direct real-time structure-function correlation studies of biological macromolecules. © 1997 John Wiley & Sons, Inc. Int J Imaging Syst Technol, 8, 293–300, 1997     

Nanowire probes for high resolution combined scanning electrochemical microscopy - atomic force microscopy

We describe a method for the production of nanoelectrodes at the apex of atomic force microscopy (AFM) probes. The nanoelectrodes are formed from single-walled carbon nanotube AFM tips which act as the template for the formation of nanowire tips through sputter coating with metal. Subsequent deposition of a conformal insulating coating, and cutting of the probe end, yields a disk-shaped nanoelectrode at the AFM tip apex whose diameter is defined by the amount of metal deposited. We demonstrate that these probes are capable of high-resolution combined electrochemical and topographical imaging. The flexibility of this approach will allow the fabrication of nanoelectrodes of controllable size and composition, enabling the study of electrochemical activity at the nanoscale.     

Protein crystals as scanned probes for recognition atomic force microscopy

Lysozyme crystal growth has been localized at the tip of a conventional silicon nitride cantilever through seeded nucleation. After cross-linking with glutaraldehyde, lysozyme protein crystal tips image gold nanoparticles and grating standards with a resolution comparable to that of conventional tips. Force spectra between the lysozyme crystal tips and surfaces covered with antilysozyme reveal an adhesion force that drops significantly upon blocking with free lysozyme, thus confirming that lysozyme crystal tips can detect molecular recognition interactions.     

Submicrosecond time resolution atomic force microscopy for probing nanoscale dynamics

We propose, simulate, and experimentally validate a new mechanical detection method to analyze atomic force microscopy (AFM) cantilever motion that enables noncontact discrimination of transient events with ~100 ns temporal resolution without the need for custom AFM probes, specialized instrumentation, or expensive add-on hardware. As an example application, we use the method to screen thermally annealed poly(3-hexylthiophene):phenyl-C(61)-butyric acid methyl ester photovoltaic devices under realistic testing conditions over a technologically relevant performance window. We show that variations in device efficiency and nanoscale transient charging behavior are correlated, thereby linking local dynamics with device behavior. We anticipate that this method will find application in scanning probe experiments of dynamic local mechanical, electronic, magnetic, and biophysical phenomena.     

Routine and timely sub-picoNewton force stability and precision for biological applications of atomic force microscopy

Force drift is a significant, yet unresolved, problem in atomic force microscopy (AFM). We show that the primary source of force drift for a popular class of cantilevers is their gold coating, even though they are coated on both sides to minimize drift. Drift of the zero-force position of the cantilever was reduced from 900 nm for gold-coated cantilevers to 70 nm (N = 10; rms) for uncoated cantilevers over the first 2 h after wetting the tip; a majority of these uncoated cantilevers (60%) showed significantly less drift (12 nm, rms). Removing the gold also led to ～10-fold reduction in reflected light, yet short-term (0.1-10 s) force precision improved. Moreover, improved force precision did not require extended settling; most of the cantilevers tested (9 out of 15) achieved sub-pN force precision (0.54 ± 0.02 pN) over a broad bandwidth (0.01-10 Hz) just 30 min after loading. Finally, this precision was maintained while stretching DNA. Hence, removing gold enables both routine and timely access to sub-pN force precision in liquid over extended periods (100 s). We expect that many current and future applications of AFM can immediately benefit from these improvements in force stability and precision.     

原子力声显微镜的原理及应用

原子力声显微镜结合了超声检测技术的三维成像能力与原子力显微镜的纳米尺度成像的近场显微技术。它在商用的原子力显微镜设备的基础上加以压电超声传感器产生声激励,并使用锁相放大器对数据进行收集分析,既可得到三维的纳米级的清晰形貌图,又能通过建模分析样品表面的接触刚度及样品的弹性模量。目前,原子力显微镜被广泛应用于材料领域,用于检测样品的机械性能,比如样品的接触刚度、薄膜高分子材料的弹性模量,同时还运用于医学生物领域,用于观察细胞的超微结构及其表面和亚表面的弹性模量等。     

Specific aptamer-protein interaction studied by atomic force microscopy

Aptamers are a new class of synthetic DNA/RNA oligonucleotides generated from in vitro selection to selectively bind with various molecules. Due to their molecular recognition capability for proteins, aptamers are becoming promising reagents in protein detection and new drug development. In this study, the specific interaction between the protein immunoglobulin E (IgE) and its 37-nt aptamer has been measured directly by atomic force microscopy. The single-molecule unbinding force between IgE and the aptamer is determined using the Poisson statistical method. The individual unbinding force between IgE and its monoclonal antibody has also been obtained and compared to that between IgE and the aptamer. The results reveal the high affinity of the aptamer to protein, which could match or even surpass that of the antibody to its antigen.     

Wavelet-transform processing of images in atomic force microscopy

Use of the wavelet transform is suggested for the processing of images obtained with a scanning atomic force microscope (AFM). Efficacy of the proposed method is illustrated by the results of numerical modeling of the AFM images. The wavelet transform can be also employed for the processing of images in optical near-field, electron tunneling, and magnetic force microscopies.     

Precise control of nanofabrication by atomic force microscopy

With an aim of the precise control of the anodic oxidation process by atomic force microscopy, the technical improvement has been carried out based on the mechanism studies. The accuracy and reliability of the nanofabrication have been improved by the combination of ambient humidity control, improvement of instrumental performance and meniscus lifetime control. In parallel, the mechanism study has been proceeded through the detection of Faradaic current. The in situ Faradaic current detection of the nano-oxidation process can actually work as a sensitive monitor for the nano-oxidation process with a high reliability. From an engineering viewpoint with an eye to practical applications, controllable physical parameters which affect on the product size are enumerated to consider what we should do to raise the precision of nano-oxidation. Then the fast fabrication in a large area by a patchwork method, Faradaic current detection during oxidation-reduction reaction, and nanofabrication by current-control are shown as examples.