Enhanced pulsed magneto-motive ultrasound imaging using superparamagnetic nanoclusters

Recently, pulsed magneto-motive ultrasound (pMMUS) imaging augmented with ultra-small magnetic nanoparticles has been introduced as a tool capable of imaging events at molecular and cellular levels. The sensitivity of a pMMUS system depends on several parameters, including the size, geometry and magnetic properties of the nanoparticles. Under the same magnetic field, larger magnetic nanostructures experience a stronger magnetic force and produce larger displacement, thus improving the sensitivity and signal-to-noise ratio (SNR) of pMMUS imaging. Unfortunately, large magnetic iron-oxide nanoparticles are typically ferromagnetic and thus are very difficult to stabilize against colloidal aggregation. In the current study we demonstrate improvement of pMMUS image quality by using large size superparamagnetic nanoclusters characterized by strong magnetization per particle. Water-soluble magnetic nanoclusters of two sizes (15 and 55 nm average size) were synthesized from 3 nm iron precursors in the presence of citrate capping ligand. The size distribution of synthesized nanoclusters and individual nanoparticles was characterized using dynamic light scattering (DLS) analysis and transmission electron microscopy (TEM). Tissue mimicking phantoms containing single nanoparticles and two sizes of nanoclusters were imaged using a custom-built pMMUS imaging system. While the magnetic properties of citrate-coated nanoclusters are identical to those of superparamagnetic nanoparticles, the magneto-motive signal detected from nanoclusters is larger, i.e. the same magnetic field produced larger magnetically induced displacement. Therefore, our study demonstrates that clusters of superparamagnetic nanoparticles result in pMMUS images with higher contrast and SNR.     

Residue-specific immobilization of protein molecules by size-selected clusters

The atomic force microscope (AFM), operating in contact mode, has been employed in buffer solution to study two proteins; (i) green fluorescent protein (GFP), from the hydromedusan jellyfish Aequorea victoria; and (ii) human oncostatin M (OSM), in the presence of size-selected gold nanoclusters pinned on to a highly oriented pyrolytic graphite substrate. The AFM images have revealed immobilization of single molecules of OSM, which are strongly bound to the gold nanoclusters. Conversely, no strong immobilization has been observed for the GFP, as these molecules were easily displaced by the scanning tip. The contrasting behaviour of the two proteins can be explained by the exposed molecular surface area of their cysteine residues as modelled on the basis of their respective X-ray crystallographic data structures. GFP contains two cysteine residues, but neither is readily available to chemisorb on the gold clusters, because the cysteines are largely inaccessible from the surface of the protein. In contrast, OSM has a total of five cysteine residues, with different degrees of accessibility, which make the protein amenable to anchoring on the nanoclusters. Statistical analysis of the height of the OSM molecules bound to the nanoclusters is in accordance with crystallographic data, and suggests various configurations of the proteins on the clusters, associated with the presence of different cysteine anchoring sites. These results suggest that the three-dimensional conformation of protein molecules is preserved when they are chemisorbed to size-selected gold clusters, thus opening a new route towards oriented immobilization of individual protein molecules.     

Towards full-structure determination of bimetallic nanoparticles with an aberration-corrected electron microscope

To fully understand the properties of functional nanostructures such as catalytic nanoclusters, it is necessary to know the positions of all the atoms in the nanostructure. The catalytic properties of metal nanoclusters can often be improved by the addition of a second metal, but little is known about the role of the different metals in these bimetallic catalysts, or about their interactions with each other and the support material. Here we show that aberration-corrected scanning transmission electron microscopy of supported rhodium-iridium clusters, combined with dynamic multislice image simulations, can identify individual atoms, map the full structure, and determine changes in the positions of metal atoms in sequential images. This approach could help in the development of new and improved catalysts and other functional nanostructures.     

Discrete charging effects in gold nanoclusters grown on self-assembled monolayers

Single electron charging effects were observed for gold nanoclusters grown on octanedithiol self-assembled monolayers by scanning tunneling microscopy and X-ray photoelectron spectroscopy (XPS). Strong interaction of gold with the terminal sulfur atoms of dithiol molecules on Au(111) suppresses effectively the penetration of deposited gold atoms through the dithiol layer and results in the formation of uniform metal nanoclusters. Decoupling of the clusters from Au(111) by the octanedithiol layer and the small self-capacitance of the nanoclusters realize the observation of the Coulomb blockade in scanning tunneling spectroscopy and the Au 4f core level shifts in XPS at room temperature. Both phenomena originate from a common physics, the Coulomb energy of charged particles.     

Discrete charging effects in gold nanoclusters grown on self-assembled monolayers

Single electron charging effects were observed for gold nanoclusters grown on octanedithiol self-assembled monolayers by scanning tunneling microscopy and X-ray photoelectron spectroscopy (XPS). Strong interaction of gold with the terminal sulfur atoms of dithiol molecules on Au(111) suppresses effectively the penetration of deposited gold atoms through the dithiol layer and results in the formation of uniform metal nanoclusters. Decoupling of the clusters from Au(111) by the octanedithiol layer and the small self-capacitance of the nanoclusters realize the observation of the Coulomb blockade in scanning tunneling spectroscopy and the Au 4f core level shifts in XPS at room temperature. Both phenomena originate from a common physics, the Coulomb energy of charged particles.     

Method for reduction of background artifacts of images in scanning holography with a Fresnel-zone-plate coded aperture

Near-infrared scanning holography with a Fresnel zone plate (FZP) coded aperture has potential applications in imaging through turbid media. However, the nonnegative intensity-distribution function of the FZP coded aperture introduces the background artifacts into the reconstructed images, reducing the contrast and the signal-to-noise ratio (SNR) of the images. A novel method termed as the composite hologram is proposed to reduce the artifacts. The computer simulations showed that the contrast and the SNR of the reconstructed images had improvements of at least 50.2% and 5.58-dB, respectively, compared with the conventional method. The composite hologram of a metal ring with a 6.0-mm diameter made by a wire with a 0.4-mm diameter immersing in 1% intralipid solution was recorded, and the reconstruction was performed numerically. The experimental results demonstrated that the contrast and the SNR of the reconstructed image had improvements of at least 32.3% and 2.51-dB, respectively.     

Synthesis of core-shell nanoclusters with high magnetic moment for biomedical applications

Biocompatible magnetic nanoparticles have been found to be promising in several biomedical applications for tagging, imaging, sensing, and separation in recent years. Most magnetic particles or beads currently used in biomedical applications are based on ferromagnetic iron oxides with very low specific magnetic moments of about 20-30 emu/g. Here, we report a new approach to synthesize monodispersive core-shell nanostructured clusters with high specific magnetic moments above 200 emu/g. The Fe nanoclusters, ranging in size from 2 to 100 nm, are produced from a newly developed cluster source and go to a deposition chamber, where a chemical reaction starts, and the nanoclusters are coated with Fe oxides. High-resolution transmission electron microscopy images show the coatings are very uniform. The core-shell nanoclusters are superparamagnetic at room temperature for sizes less than 12 nm, and have the coercivity of about 1.5 kOe at low temperature (5 K).     

Structure of the Au-Rh bimetallic system formed on titanate nanowires and nanotubes

Au, Rh and Au-Rh nanoclusters were studied on one-dimensional titania nanostructures by X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and infrared spectroscopy (FT-IR). On titanate nanowire and tube supports the gold 4f_7/2 XP emission appeared after reduction at 83.6 eV and 85.6 eV indicating two different sizes or chemical environments of gold nanoclusters. Small clusters also developed in rhodium containing samples besides the pure metallic state. Upon CO adsorption on the 1% Rh/titanate nanostructures the IR stretching frequencies characteristic of the twin (geminal) form were dominant, whereas bimetallic nanosystems featured a pronounced linear CO stretching vibration. At the same time the highest binding energy state disappeared almost completely indicating the enlargement of nanoclusters which was in agreement with SEM results. Very likely “core-shell” bimetallic clusters form, where gold covers the rhodium.     

Techniques for imaging human metaphase chromosomes in liquid conditions by atomic force microscopy

The purpose of this study was to obtain three-dimensional images of wet chromosomes by atomic force microscopy (AFM) in liquid conditions. Human metaphase chromosomes-obtained either by chromosome spreads or by an isolation technique-were observed in a dynamic mode by AFM in a buffer solution. Under suitable operating conditions with a soft triangular cantilever (with the spring constant of 0.08-0.4?N?m(-1)), clear images of fixed chromosomes in the chromosome spread were obtained by AFM. For imaging isolated chromosomes with the height of more than 400?nm, a cantilever with a high aspect ratio probing tip was required. The combination of a Q-control system and the sampling intelligent scan (SIS) system in dynamic force mode AFM was useful for obtaining high-quality images of the isolated chromosomes, in which globular or cord-like structures about 50?nm thick were clearly observed on the surface of each chromatid.     

Rapid and multimodal <Emphasis Type="Italic">in vivo</Emphasis> bioimaging of cancer cells through <Emphasis Type="Italic">in situ</Emphasis> biosynthesis of Zn&;Fe nanoclusters

Early diagnosis remains highly important for efficient cancer treatment,and hence,there is significant interest in the development of effective imaging strategies.This work reports a new multimodal bioimaging method for accurate and rapid diagnosis of cancer cells by introducing aqueous Fe2+ and Zn2+ ions into cancer cells (i.e.,HeLa,U87,and HepG2 cancer cells).We found that the biocompatible metal ions Fe2+ and Zn2+ forced the cancer cells to spontaneously synthesize fluorescent ZnO nanoclusters and magnetic Fe3O4 nanoclusters.These clusters could then be used for multimodal cancer imaging by combining fluorescence imaging with magnetic resonance imaging and computed tomography imaging.Meanwhile,for normal cells (i.e.,L02) and tissues,neither fluorescence nor any other obvious difference could be detected between preand post-injection.This multimodal bioimaging strategy based on the in situ biosynthesized Zn&Fe oxide nanoclusters might therefore be useful for early cancer diagnosis and therapy.     

Luminescent metal nanoclusters: controlled synthesis and functional applications

Luminescent metal nanoclusters that consist of only several, to tens of, metal atoms and which possess sizes comparable to the Fermi wavelength of electrons have recently attracted significant attention. This new class of luminescent materials not only provides the missing link between atomic and nanoparticle behaviors in metals but also they present abundant novel information for the development of new applicable material systems to meet urgent needs in many areas (such as ultrasensitive sensors for heavy metals, bioimaging, as well as information technology) mainly because of their attractive characteristics, including ultra-small size, good dispersibility, excellent biocompatibility and photostability. In this review, we summarize recent advances in the controlled synthesis and application of luminescent metal nanoclusters, with a particular emphasis on Pt, Mo, Bi and alloy clusters. We also speculate on their future and discuss potential developments for their use in sensors, bioimaging and energy harvesting and conversion.     

Nanoscopic imaging of human chromosomes via a scanning near-field optical/atomic-force microscopy (SNOAM)

Scanning near-field optical/atomic-force microscopy (SNOAM) provided us with simultaneous topographic and fluorescence images of human chromosomes. The SNOAM uses a bent optical fiber simultaneously as a dynamic mode atomic force microscopy cantilever. Optical resolution was approximately 50–100 nm in fluorescence mode. Conventional karyotyping information was linked with SNOAM topographic analyses such as location of centromere and length of individual chromosomes. The height profile clearly indicated higher teromere regions. The SNOAM fluorescence images were different shapes from topographic images probably due to results from the combination of fluorescence dye and chromosome DNA.     

Mass spectrometry and dynamics of gold adatoms observed on the surface of size-selected Au nanoclusters

We report the imaging, mass spectrum, and dynamical behavior of adatoms and small clusters observed on the surface facets of size-selected, truncated octahedral gold clusters, Au(N) (N = 923 ± 23), via aberration-corrected scanning transmission electron microscopy. Our quantitative atom counting measurements show that most (~70%) of the species on the surface are single Au adatoms. Such species are now proposed as key elements of the atomic structure of both monolayer-protected nanoclusters (nanoparticles) and self-assembled monolayers and may also play a role in gold nanocatalysis. The adatoms are found on both {100} and {111} facets with similar probabilities.     

Ultra-small fluorescent metal nanoclusters: Synthesis and biological applications

Recent advances in nanotechnology have given rise to a new class of fluorescent labels, fluorescent metal nanoclusters, e.g., Au and Ag. These nanoclusters are of significant interest because they provide the missing link between atomic and nanoparticle behavior in metals. Composed of a few to a hundred atoms, their sizes are comparable to the Fermi wavelength of electrons, resulting in molecule-like properties including discrete electronic states and size-dependent fluorescence. Fluorescent metal nanoclusters have an attractive set of features, such as ultrasmall size, good biocompatibility and excellent photostability, making them ideal fluorescent labels for biological applications. In this review, we summarize synthesis strategies of water-soluble fluorescent metal nanoclusters and their optical properties, highlight recent advances in their application for ultrasensitive biological detection and fluorescent biological imaging, and finally discuss current challenges for their potential biomedical applications.     

Native tissue imaging at superharmonic frequencies

The second harmonic imaging mode has been adapted to image tissue and shown considerable improvements in image quality in several applications compared to the fundamental mode. The improvements were attributed to the effects of wave distortion due to nonlinear propagation in tissue. However, imaging tissue at the second harmonic frequency only has various drawbacks. Because the energy in the second harmonic frequency band is much lower than that in the fundamental frequency band, there must be excellent sensitivity and dynamic range in the receiving system to achieve an acceptable amount of signal-to-noise ratio. To increase the sensitivity, the spectral overlap between the fundamental and the second harmonic has to be diminished, which in return deteriorates the imaging resolution. Consequently, a trade-off is mandatory between resolution and sensitivity. Using simulations and measurements, we show that, at appropriate scanning acoustic settings, higher harmonics are generated in tissue. The higher harmonics represent additional, relevant information for tissue imaging and characterization. An elegant way to take advantage of the higher harmonics and to bring all the information together is to combine and incorporate all the multiple higher harmonics into a single component that we call the superharmonic component. Using a newly developed array transducer having a wide frequency band, B-mode images of a phantom were made in the superharmonic mode transmitting at 1.2 MHz. These images have exceptionally improved clarity and yield a dramatically cleaner and sharper contrast between the different structures being imaged. In addition to increased signal-to-noise ratio, superharmonic imaging shows better contrast and axial resolution as well as acceptable penetration depth.     

硫醇保护的银簇制备及其荧光检测应用的进展EI北大核心CSCD

贵金属纳米簇具有独特的电子结构和荧光特性,可以作为荧光探针,广泛应用于生物标记、离子检测等领域。本文综述了硫醇保护的银簇的制备方法,包括自下而上法和自上而下法,重点从优化反应的还原动力过程,选择优良的硫醇配体,改变体系的pH值,严格控制反应过程中的刻蚀时间和反应温度等方面,介绍了关于硫醇保护的银簇制备的研究现状,对进一步研究提供了思路。同时,基于硫醇保护的银簇优异的荧光性质,介绍了在检测Cu^2+,Hg^2+,I^-等离子以及半胱氨酸等小分子方面的研究进展。最后指出,提高金属纳米簇的荧光量子产率和安全性,深入研究金属纳米簇与重金属离子、生物大分子的反应机理,探究高纯度、多样性的合金簇或过渡金属纳米簇的合成方法,实现高效率的基于硫醇保护的银簇荧光传感材料的制备是未来研究中的热门方向。     

Noncontact electrochemical imaging with combined scanning electrochemical atomic force microscopy

Combined scanning electrochemical atomic force microscopy (SECM-AFM) is a recently introduced scanned probe microscopy technique where the probe, which consists of a tip electrode and integrated cantilever, is capable of functioning as both a force sensor, for topographical imaging, and an ultramicroelectrode for electrochemical imaging. To extend the capabilities of the technique, two strategies for noncontact amperometric imaging-in conjunction with contact mode topographical imaging-have been developed for the investigation of solid-liquid interfaces. First, SECM-AFM can be used to image an area of the surface of interest, in contact mode, to deduce the topography. The feedback loop of the AFM is then disengaged and the stepper motor employed to retract the tip a specified distance from the sample, to record a current image over the same area, but with the tip held in a fixed x-y plane above the surface. Second, Lift Mode can be employed, where a line scan of topographical AFM data is first acquired in contact mode, and the line is then rescanned to record SECM current data, with the tip maintained at a constant distance from the target interface, effectively following the contours of the surface. Both approaches are exemplified with SECM feedback and substrate generation-tip collection measurements, with a 10-microm-diameter Pt disk UME serving as a model substrate. The approaches described allow electrochemical images, acquired with the tip above the surface, to be closely correlated with the underlying topography, recorded with the tip in intimate contact with the surface.     

PTCDA molecules on an InSb(001) surface studied with atomic force microscopy

PTCDA (3,4,9,10-perylene-tetracarboxylic-dianhydride) molecular structures assembled on an InSb(001) c(8 × 2) reconstructed surface have been studied using frequency modulated atomic force microscopy. The high-resolution imaging of the structures is possible through repulsive interactions, using the constant height scanning mode. During initial stages of growth the [110] diffusion channel dominates as indicated by formation of long PTCDA molecular chains parallel to the [110] crystallographic direction on the InSb surface. For a single monolayer coverage a wetting layer of PTCDA is formed. Finally it is shown that the PTCDA/InSb is a promising system for building molecular nanostructures by manipulation of single molecules with the AFM tip.     

金属纳米团簇结合能的计算模型

金属团簇在尺寸较小时一般为多面体形.通过考虑团簇的内部原子、面上原子、棱上原子以及顶点原子对团簇结合能的贡献,将键能模型推广至纳米团簇体系.计算表明,虽然棱上原子以及顶点原子对大尺寸微粒的结合能贡献不大,但对于团簇的结合能计算则特别重要.推广后的键能模型可以被用来研究不同形状团簇的结构稳定性和熔化热力学等.     

One-pot synthesis of aptamer-functionalized silver nanoclusters for cell-type-specific imaging

As an emerging category of fluorescent metal nanoclusters, oligonucleotide-templated silver nanoclusters (Ag NCs) have attracted a lot of interest and have shown wide application in biorelated disciplines. However, the weak fluorescence emission and poor permeability to cell membranes tethered further intracellular applications of Ag NCs. AS1411 is an antiproliferative G-rich phosphodiester oligonucleotide and currently an anticancer agent under phase II clinical trials. Herein, we present a strategy to synthesize AS1411-functionalized Ag NCs with excellent fluorescence through a facile one-pot process. Confocal laser scanning microscopy and Z-axis scanning confirmed that the AS1411-functionalized Ag NCs could be internalized into MCF-7 human breast cancer cells and were able to specifically stain nuclei with red color. To our surprise, 3-[4,5-dimethylthiazol-z-yl]-2,5-diphenyltetrazolium bromide (MTT) assay demonstrated the Ag NCs were cytocompatible and showed better inhibition effects than pure AS1411 on MCF-7 human breast cancer cells. In addition, a universal design of the oligonucleotide scaffold for synthesis of Ag NCs was extended to other aptamers, such as Sgc8c and mucin 1 aptamer. Due to the facile synthesis procedure and capability of specific target recognition, this fluorescent platform will potentially broaden the applications of Ag NCs in biosensing and biological imaging.