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In this work, we report on the improvement of microarray sensitivity provided by a crystalline silicon substrate coated with thermal silicon oxide functionalized by a polymeric coating. The improvement is intended for experimental procedures and instrumentations typically involved in microarray technology, such as fluorescence labeling and a confocal laser scanning apparatus. The optimized layer of thermally grown silicon oxide (SiO(2)) of a highly reproducible thickness, low roughness, and fluorescence background provides fluorescence intensification due to the constructive interference between the incident and reflected waves of the fluorescence radiation. The oxide surface is coated by a copolymer of N,N-dimethylacrylamide, N-acryloyloxysuccinimide, and 3-(trimethoxysilyl)propyl methacrylate, copoly(DMA-NAS-MAPS), which forms, by a simple and robust procedure, a functional nanometric film. The polymeric coating with a thickness that does not appreciably alter the optical properties of the silicon oxide confers to the slides optimal binding specificity leading to a high signal-to-noise ratio. The present work aims to demonstrate the great potential that exists by combining an optimized reflective substrate with a high performance surface chemistry. Moreover, the techniques chosen for both the substrate and surface chemistry are simple, inexpensive, and amenable to mass production. The present application highlights their potential use for diagnostic applications of real clinical relevance. The coated silicon slides, tested in protein and peptide microarrays for detection of specific antibodies, lead to a 5-10-fold enhancement of the fluorescence signals in comparison to glass slides.

The self-assembling of the amyloid β (Aβ) peptide into neurotoxic aggregates is considered a central event in the pathogenesis of Alzheimer's disease (AD). Based on the "amyloid hypothesis", many efforts have been devoted to designing molecules able to halt disease progression by inhibiting Aβ self-assembly. Here, we combine biophysical (ThT assays, TEM and AFM imaging), biochemical (WB and ESI-MS), and computational (all-atom molecular dynamics) techniques to investigate the capacity of four optically pure components of the natural product silymarin (silybin A, silybin B, 2,3-dehydrosilybin A, 2,3-dehydrosilybin B) to inhibit Aβ aggregation. Despite TEM analysis demonstrated that all the four investigated flavonoids prevent the formation of mature fibrils, ThT assays, WB and AFM investigations showed that only silybin B was able to halt the growth of small-sized protofibrils thus promoting the formation of large, amorphous aggregates. Molecular dynamics (MD) simulations indicated that silybin B interacts mainly with the C-terminal hydrophobic segment MVGGVV of Aβ40. Consequently to silybin B binding, the peptide conformation remains predominantly unstructured along all the simulations. By contrast, silybin A interacts preferentially with the segments LVFF and NKGAII of Aβ40 which shows a high tendency to form bend, turn, and β-sheet conformation in and around these two domains. Both 2,3-dehydrosilybin enantiomers bind preferentially the segment LVFF but lead to the formation of different small-sized, ThT-positive Aβ aggregates. Finally, in vivo studies in a transgenic Caenorhabditis elegans strain expressing human Aβ indicated that silybin B is the most effective of the four compounds in counteracting Aβ proteotoxicity. This study underscores the pivotal role of stereochemistry in determining the neuroprotective potential of silybins and points to silybin B as a promising lead compound for further development in anti-AD therapeutics.

An experimental study of the Si 2p XPS spectrum at different take-off angles of atomically flat, hydrogenterminated 1 × 1 Si(100) is reported. The observed spectrum can be described accurately by considering three additional contributions to the spectrum of elemental silicon. Each contribution is attributed to a chemical state of silicon on the basis of its chemical shift with respect to elemental silicon and the depth of the region where it was originated.

Here we show the fabrication of the Luminometric Sub-nanoliter Droplet-to-droplet Array (LUMDA chip) by inkjet printing. The chip is easy to be implemented and allows for a multiplexed multi-step biochemical assay in sub-nanoliter liquid spots. This concept is here applied to the integral membrane enzyme CYP3A4, i.e. the most relevant enzymatic target for phase I drug metabolism, and to some structurally-related inhibitors.

The definition of features on the nanometre length scale (NLS) is impossible via conventional lithography, but can be done using extreme ultraviolet, synchrotron-radiation, or electron beam lithography. However, since these techniques are very expensive and still in their infancy, their exploitation in integrated circuit (IC) processing is still highly putative. Geometries on the NLS can however be produced with relative ease using the spacer patterning technique, i.e. transforming vertical features (like film thickness) in the vicinity of a step of a sacrificial layer into horizontal features. The ultimate length that can be produced in this way is controlled by the steepness of the step defining the sacrificial layer, the uniformity of the deposited or grown films, and the anisotropy of its etching. While useful for the preparation of a few devices with special needs, the above trick does not allow by itself the development of a nanotechnology where each layer useful for defining the circuit should be on the NLS and aligned on the underlying geometries with tolerances on the NLS. Setting up such a nanotechnology is a major problem which will involve the IC industry in the post-Roadmap era. Irrespective of the detailed structure of the basic constituents (molecules, supramolecular structures, clusters, etc), ICs with nanoscopic active elements can hardly be prepared without the ability to produce arrays of conductive strips with pitch on the NLS. This work is devoted to describing a scheme (essentially based on the existing microelectronic technology) for their production without the use of advanced lithography and how it can be arranged to host molecular devices.

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This work presents a study based on x-ray photoelectron spectroscopy of the reaction of hydrogen-terminated silicon with 1-alkynes as a route for the functionalization of the (100) surface of silicon. The study (i) demonstrates that the grafting of hydrocarbon moieties is possible by simple exposure of the silicon surface to a liquid alkyne, (ii) shows that the derivatization protects the silicon against oxidation in air, (iii) indicates that the process occurs via hydrosilation of the alkyne at the hydrogen-terminated surface and (iv) suggests that grafted moieties contain in large part an unreacted π bond.