Atomic Force Microscopy Nanomanipulation Research Articles

Review: Advanced Atomic Force Microscopy Modes for Biomedical Research

Visualization of biomedical samples in their native environments at the microscopic scale is crucial for studying fundamental principles and discovering biomedical systems with complex interaction. The study of dynamic biological processes requires a microscope system with multiple modalities, high spatial/temporal resolution, large imaging ranges, versatile imaging environments and ideally in-situ manipulation capabilities. Recent development of new Atomic Force Microscopy (AFM) capabilities has made it such a powerful tool for biological and biomedical research. This review introduces novel AFM functionalities including high-speed imaging for dynamic process visualization, mechanobiology with force spectroscopy, molecular species characterization, and AFM nano-manipulation. These capabilities enable many new possibilities for novel scientific research and allow scientists to observe and explore processes at the nanoscale like never before. Selected application examples from recent studies are provided to demonstrate the effectiveness of these AFM techniques.

Mechanism-Independent Manipulation of Single-Wall Carbon Nanotubes with Atomic Force Microscopy Tip.

Atomic force microscopy (AFM) based nanomanipulation can align the orientation and position of individual carbon nanotubes accurately. However, the flexible deformation during the tip manipulation modifies the original shape of these nanotubes, which could affect its electrical properties and reduce the accuracy of AFM nanomanipulation. Thus, we developed a protocol for searching the synergistic parameter combinations to push single-wall carbon nanotubes (SWCNTs) to maintain their original shape after manipulation as far as possible, without requiring the sample physical properties and the tip-manipulation mechanisms. In the protocol, from a vast search space of manipulating parameters, the differential evolution (DE) algorithm was used to identify the optimal combinations of three parameters rapidly with the DE algorithm and the feedback of the length ratio of SWCNTs before and after manipulation. After optimizing the scale factor F and crossover probability Cr, the values F = 0.4 and Cr = 0.6 were used, and the ratio could reach 0.95 within 5–7 iterations. A parameter region with a higher length ratio was also studied to supply arbitrary pushing parameter combinations for individual manipulation demand. The optimal pushing parameter combination reduces the manipulation trajectory and the tip abrasion, thereby significantly improving the efficiency of tip manipulation for nanowire materials. The protocol for searching the best parameter combinations used in this study can also be extended to manipulate other one-dimensional nanomaterials.

Atomic Force Microscopy Nanomanipulation by Confocal Raman Multiwavelength Spectroscopy: Application at the Monitoring of Resonance Profile Excitation Changes of Manipulated Carbon Nanotube

This paper explores the possibilities offered by coupling AFM nano-manipulation with Resonance Raman Excitation Profile approaches. We apply this method to nanostructures produced by AFM nano-manipulation. The experimental demonstration is made on the interaction between two single-wall carbon nanotubes, one semiconducting and the other metallic. The measurement is analyzed and discussed in terms of resonance shifts and broadening of the electronic transition.

Time-Lapse Atomic Force Microscopy Reveals New End Take Off (Neto) Dynamics in Mycobacteria

Tuberculosis is a lung infection caused by Mycobacterium tuberculosis. One third of the world population is thought to be infected. Antibiotic treatment with antibiotics lasts 6 month, which is difficult to achieve in low-income countries. The uncommon ability of tuberculosis bacteria to persist during long periods is linked to various factors, one of which potentially being cell growth asymmetry. However, growth symmetry or asymmetry of mycobacteria remains a controversial topic as opposing descriptions have been reported in the literature. Observing bacterial growth at the single cell level is inherently challenging due to the diffraction limit of optical microscopes and the small size of the cells. We built a new dedicated platform for long-term, correlated Atomic Force Microscopy (AFM) and fluorescence microscopy and obtained time-lapses of bacterial growth at an unprecedented resolution. Surprisingly, the AFM high-resolution time-lapses did not match any of the two previously reported models of pure symmetry and pure asymmetry. Mycobacterial pole growth dynamics was rather an intermediate between the two, reminiscent of the well-known “new end take off” mechanism for fission yeast. Using AFM nanomanipulation we show that growth asymmetry is not a physical occlusion phenomenon, but is inherent to mycobacterial growth. Finally, using fluorescent photoconversion microscopy we identify biomolecular mechanisms linked to growth asymmetry, which in the future could be used to develop novel treatments for tuberculosis infection.

In situ scattering of single gold nanorod coupling with monolayer transition metal dichalcogenides.

We investigated in situ the interaction between a single gold nanorod and monolayer transition metal dichalcogenides (TMDCs) by atomic force microscopy nanomanipulation and single-particle spectroscopy. We observed that the resonant scattering peak of the hybrid redshifted, the full width at half maximum of the scattering resonance narrowed and the scattering intensity increased compared with those of the same nanorod before coupling with monolayer TMDCs. These results were understood with the aid of finite-difference time-domain simulations, the Fano model, and the classical oscillator model. Also, the spectral features varied with the distance between the nanorod and TMDCs, and the interaction was mainly attributed to the resonant energy transfer effect. Our findings clarify the influence of TMDCs on the plasmonic resonance and contribute to a deeper understanding of the plasmon exciton interaction. These results are beneficial for the optimization of plasmonic nanostructure-TMDC hybrids and their corresponding applications.

Universal deformation pathways and flexural hardening of nanoscale 2D-material standing folds

In the present work, we use atomic force microscopy nanomanipulation of 2D-material standing folds to investigate their mechanical deformation. Using graphene, h-BN and talc nanoscale wrinkles as testbeds, universal force–strain pathways are clearly uncovered and well-accounted for by an analytical model. Such universality further enables the investigation of each fold bending stiffness κ as a function of its characteristic height h0. We observe a more than tenfold increase of κ as h0 increases in the 10–100 nm range, with power-law behaviors of κ versus h0 with exponents larger than unity for the three materials. This implies anomalous scaling of the mechanical responses of nano-objects made from these materials.

Assembly of \u201c3D\u201d plasmonic clusters by \u201c2D\u201d AFM nanomanipulation of highly uniform and smooth gold nanospheres

Atomic force microscopy (AFM) nanomanipulation has been viewed as a deterministic method for the assembly of plasmonic metamolecules because it enables unprecedented engineering of clusters with exquisite control over particle number and geometry. Nevertheless, the dimensionality of plasmonic metamolecules via AFM nanomanipulation is limited to 2D, so as to restrict the design space of available artificial electromagnetisms. Here, we show that “2D” nanomanipulation of the AFM tip can be used to assemble “3D” plasmonic metamolecules in a versatile and deterministic way by dribbling highly spherical and smooth gold nanospheres (NSs) on a nanohole template rather than on a flat surface. Various 3D plasmonic clusters with controlled symmetry were successfully assembled with nanometer precision; the relevant 3D plasmonic modes (i.e., artificial magnetism and magnetic-based Fano resonance) were fully rationalized by both numerical calculation and dark-field spectroscopy. This templating strategy for advancing AFM nanomanipulation can be generalized to exploit the fundamental understanding of various electromagnetic 3D couplings and can serve as the basis for the design of metamolecules, metafluids, and metamaterials.

Interplay Between Optical Bianisotropy and Magnetism in Plasmonic Metamolecules.

The smallness of natural molecules and atoms with respect to the wavelength of light imposes severe limits on the nature of their optical response. For example, the well-known argument of Landau and Lifshitz and its recent extensions that include chiral molecules show that the electric dipole response dominates over the magneto-electric (bianisotropic) and an even smaller magnetic dipole optical response for all natural materials. Here, we experimentally demonstrate that both these responses can be greatly enhanced in plasmonic nanoclusters. Using atomic force microscopy nanomanipulation technique, we assemble a plasmonic metamolecule that is designed for strong and simultaneous optical magnetic and magneto-electric excitation. Angle-dependent scattering spectroscopy is used to disentangle the two responses and to demonstrate that their constructive/destructive interplay causes strong directional scattering asymmetry. This asymmetry is used to extract both magneto-electric and magnetic dipole responses and to demonstrate their enhancement in comparison to ordinary atomistic materials.

Controlled assembly of graphene sheets and nanotubes: Fabrication of suspended multi-element all-carbon vibrational structures

We report on the fabrication and operation of a multi-element vibrational structure consisting of two graphene mechanical resonators coupled by a nanotube beam. The whole structure is suspended. Each graphene resonator is clamped by two metal electrodes. The structure is fabricated using a combination of electron-beam lithography and atomic-force microscopy nano-manipulation. This layout allows us to detect the mechanical vibrations electrically. The measured eigenmodes are localized in either one of the graphene resonators. The coupling due to the nanotube is studied by measuring the shift of the resonance frequency of one graphene resonator as a function of the vibration amplitude of the other resonator. Coupled graphene resonators hold promise for the study of nonlinear dynamics, the manipulation of mechanical states, and quantum non-demolition measurements.

Manipulating Coupling between a Single Semiconductor Quantum Dot and Single Gold Nanoparticle

Using atomic force microscopy nanomanipulation, we position a single Au nanoparticle near a CdSe/ZnS quantum dot to construct a hybrid nanostructure with variable geometry. The coupling between the two particles is varied in a systematic and reversible manner. The photoluminescence lifetime and blinking of the same quantum dot are measured before and after assembly of the structure. In some hybrid structures, the total lifetime is reduced from about 30 ns to well below 1 ns. This dramatic change in lifetime is accompanied by the disappearance of blinking as the nonradiative energy transfer from the CdSe/ZnS quantum dot to the Au nanoparticle becomes the dominant decay channel. Both total lifetime and photoluminescence intensity changes are well described by simple analytical calculations.

Atomic Force Microscopy Nanomanipulation of Shape Persistent, Spherical, Self-Assembled Aggregates of Gold Nanoparticles

Gold (Au) nanoparticles have been synthesized that are stabilized by an organic ligand bearing a dithiolane functional group for binding to Au, an oligo(p-phenylene vinylene) (OPV) chromophoric group to drive self-assembly via π-π interactions, and a hydroxy functionality for interparticle hydrogen bonding. The OPV-Au particles reversibly self-assemble in n-heptane solution, forming shape persistent, spherical, nanometer-sized aggregates that do not collapse on a substrate. Optical absorption and transmission electron microscopy tomography studies show that the size and shape persistency can be tuned by modification of the ligands, adjustment of the core size, and variation of the concentration. The spherical assemblies can be manipulated with the tip of an atomic force microscope: an aggregate can be pushed over the surface for at least 20 times with nanometer precision and without substantial loss of material.

Design and Implementation of Motion Controllers for Atomic Force Microscopy Based Nanomanipulation Systems

Nanomanipulation with Atomic Force Microscopy (AFM) is one of the fundamental tools for nano-manufacturing. The motion control of the nanomanipulation system requires accurate feedback from the piezoelectric actuator and high frequency response from the control system. Since normal AFM control system for scanning motion is not suitable for controller of arbitrary motion, we therefore modified the hardware configuration to meet the demand of nanomanipulation control. By identifying the necessary parameters using system identification methods, we built up a new dynamic model for the modified configuration. Based on the new model and configuration, we designed and implemented a control scheme as motion controller for AFM nanomanipulation operation. The aims are to analyze various factors in the control of the AFM based nanomanipulation system. By integrating the original AFM controller with the external Linux real-time controller, we achieved a stable system with high frequency response. Several problems have been addressed based on the new control scheme, such as high frequency response, robust feedback control and non-linearity, etc. Finally this Multiple Input Single Output (MISO) system is validated by real-time nanomanipulation task. It is proved to be an effective and efficient tool for the controlling of the nanobiomanipulation operation by cutting the intercellular junction of human keratinocytes.

Nano-surgery at the leukocyte–endothelial docking site

The endothelium has an important role in controlling the extravasation of leukocytes from blood to tissues. Endothelial permeability for leukocytes is influenced by transmembrane proteins that control inter-endothelial adhesion, as well as steps of the leukocyte transmigration process. In a cascade consisting of leukocyte rolling, adhesion, firm adhesion, and diapedesis, a new step was recently introduced, the formation of a docking structure or “transmigratory cup.” Both terms describe a structure formed by endothelial pseudopods embracing the leukocyte. It has been found associated with both para- and transcellular diapedesis. The aim of this study was to characterize the leukocyte–endothelial contact area in terms of morphology and cell mechanics to investigate how the endothelial cytoskeleton reorganizes to engulf the leukocyte. We used atomic force microscopy (AFM) to selectively remove the leukocyte and then analyze the underlying cell at this specific spot. Firmly attached leukocytes could be removed by AFM nanomanipulation. In few cases, this exposed 8–12 μm wide and 1 μm deep footprints, representing the cup-like docking structure. Some of them were located near endothelial cell junctions. The interaction area did not exhibit significant alterations neither morphologically nor mechanically as compared to the surrounding cell surface. In conclusion, the endothelial invagination is formed without a net depolymerization of f-actin, as endothelial softening at the site of adhesion does not seem to be involved. Moreover, there were no cases of phagocytotic engulfment, but instead the formation of a transmigratory channel could be observed.