Jan Hilhorst

Paramagnetic Lipid-Coated Silica Nanoparticles with a Fluorescent Quantum Dot Core : A New Contrast Agent Platform for Multimodality Imaging

Silica particles as a nanoparticulate carrier material for contrast agents have received considerable attention the past few years, since the material holds great promise for biomedical applications. A key feature for successful application of this material in vivo is biocompatibility, which may be significantly improved by appropriate surface modification. In this study, we report a novel strategy to coat silica particles with a dense monolayer of paramagnetic and PEGylated lipids. The silica nanoparticles carry a quantum dot in their center and are made target-specific by the conjugation of multiple alphavbeta3-integrin-specific RGD-peptides. We demonstrate their specific uptake by endothelial cells in vitro using fluorescence microscopy, quantitative fluorescence imaging, and magnetic resonance imaging. The lipid-coated silica particles introduced here represent a new platform for nanoparticulate multimodality contrast agents.

A fluorescent, paramagnetic and PEGylated gold/silica nanoparticle for MRI, CT and fluorescence imaging

An important challenge in medical diagnostics is to design all-in-one contrast agents that can be detected with multiple techniques such as magnetic resonance imaging (MRI), X-ray computed tomography (CT), positron emission tomography (PET), single photon emission tomography (SPECT) or fluorescence imaging (FI). Although many dual labeled agents have been proposed, mainly for combined MRI/FI, constructs for three imaging modalities are scarce. Here gold/silica nanoparticles with a poly(ethylene glycol), paramagnetic and fluorescent lipid coating were synthesized, characterized and applied as trimodal contrast agents to allow for nanoparticle-enhanced imaging of macrophage cells in vitro via MRI, CT and FI, and mice livers in vivo via MRI and CT. This agent can be a useful tool in a multitude of applications, including cell tracking and target-specific molecular imaging, and is a step in the direction of truly multi-modal imaging.

In situ study of the formation mechanism of two-dimensional superlattices from PbSe nanocrystals

Oriented attachment of PbSe nanocubes can result in the formation of two-dimensional (2D) superstructures with long-range nanoscale and atomic order. This questions the applicability of classic models in which the superlattice grows by first forming a nucleus, followed by sequential irreversible attachment of nanocrystals, as one misaligned attachment would disrupt the 2D order beyond repair. Here, we demonstrate the formation mechanism of 2D PbSe superstructures with square geometry by using in situ grazing-incidence X-ray scattering (small angle and wide angle), ex situ electron microscopy, and Monte Carlo simulations. We observed nanocrystal adsorption at the liquid/gas interface, followed by the formation of a hexagonal nanocrystal monolayer. The hexagonal geometry transforms gradually through a pseudo-hexagonal phase into a phase with square order, driven by attractive interactions between the {100} planes perpendicular to the liquid substrate, which maximize facet-to-facet overlap. The nanocrystals then attach atomically via a necking process, resulting in 2D square superlattices.

Double stacking faults in convectively assembled crystals of colloidal spheres.

Using microradian X-ray diffraction, we investigated the crystal structure of convectively assembled colloidal photonic crystals over macroscopic (0.5 mm) distances. Through adaptation of Wilsons theory for X-ray diffraction, we show that certain types of line defects that are often observed in scanning electron microscopy images of the surface of these crystals are actually planar defects at 70.5 degrees angles with the substrate. The defects consist of two parallel hexagonal close-packed planes in otherwise face-centered cubic crystals. Our measurements indicate that these stacking faults cause at least 10% of stacking disorder, which has to be reduced to fabricate high-quality colloidal photonic crystals.

Three-dimensional structure and defects in colloidal photonic crystals revealed by tomographic scanning transmission X-ray microscopy.

Self-assembled colloidal crystals have attracted major attention because of their potential as low-cost three-dimensional (3D) photonic crystals. Although a high degree of perfection is crucial for the properties of these materials, little is known about their exact structure and internal defects. In this study, we use tomographic scanning transmission X-ray microscopy (STXM) to access the internal structure of self-assembled colloidal photonic crystals with high spatial resolution in three dimensions for the first time. The positions of individual particles of 236 nm in diameter are identified in three dimensions, and the local crystal structure is revealed. Through image analysis, structural defects, such as vacancies and stacking faults, are identified. Tomographic STXM is shown to be an attractive and complementary imaging tool for photonic materials and other strongly absorbing or scattering materials that cannot be characterized by either transmission or scanning electron microscopy or optical nanoscopy.

Scanning Transmission X‐Ray Microscopy as a Novel Tool to Probe Colloidal and Photonic Crystals

Photonic crystals consisting of nano- to micrometer-sized building blocks, such as multiple sorts of colloids, have recently received widespread attention. It remains a challenge, however, to adequately probe the internal crystal structure and the corresponding deformations that inhibit the proper functioning of such materials. It is shown that scanning transmission X-ray microscopy (STXM) can directly reveal the local structure, orientations, and even deformations in polystyrene and silica colloidal crystals with 30-nm spatial resolution. Moreover, STXM is capable of imaging a diverse range of crystals, including those that are dry and inverted, and provides novel insights complementary to information obtained by benchmark confocal fluorescence and scanning electron microscopy techniques.

Diffuse scattering in random-stacking hexagonal close-packed crystals of colloidal hard spheres

Microradian X-ray diffraction from sedimentary colloidal crystals is studied using synchrotron radiation with photon energies of 12.4, 27, and 38 keV. Stacking disorder in these hard-sphere crystals leads to diffuse X-ray scattering along the Bragg scattering rods normal to the randomly stacked layers. We observed the appearance of diffuse scattering, shown to be induced by multiple scattering, along the secondary Bragg rods in between the stacking-independent true Bragg reflections. This effect can be reduced by measuring at higher X-ray energies.

Slanted stacking faults and persistent face centered cubic crystal growth in sedimentary colloidal hard sphere crystals

Hard sphere crystal growth is a delicate interplay between kinetics and thermodynamics, where the former is commonly thought to favour a random hexagonal close packed structure and the latter leads to a face centered cubic crystal. In this article, we discuss the influence of slanted stacking faults on the growth of sedimentary colloidal crystals from dispersions with high initial volume fraction and particles that sediment relatively fast. We find that the presence of these persisting faults locally induces fcc structure, while defect free regions form rhcp crystals as expected for a system where kinetics dominate. These results are promising for use in epitaxial growth of colloidal crystals, where proper templating could lead to almost perfect fcc crystals with selectively incorporated defects.