Intermolecular And Surface Forces

This review encompasses the most important advances in liver functions and hepatotoxicity and analyzes which mechanisms can be studied in vitro. In a complex architecture of nested, zonated lobules, the liver consists of approximately 80 % hepatocytes and 20 % non-parenchymal cells, the latter being involved in a secondary phase that may dramatically aggravate the initial damage. Hepatotoxicity, as well as hepatic metabolism, is controlled by a set of nuclear receptors (including PXR, CAR, HNF-4α, FXR, LXR, SHP, VDR and PPAR) and signaling pathways. When isolating liver cells, some pathways are activated, e.g., the RAS/MEK/ERK pathway, whereas others are silenced (e.g. HNF-4α), resulting in up- and downregulation of hundreds of genes. An understanding of these changes is crucial for a correct interpretation of in vitro data. The possibilities and limitations of the most useful liver in vitro systems are summarized, including three-dimensional culture techniques, co-cultures with non-parenchymal cells, hepatospheres, precision cut liver slices and the isolated perfused liver. Also discussed is how closely hepatoma, stem cell and iPS cell-derived hepatocyte-like-cells resemble real hepatocytes. Finally, a summary is given of the state of the art of liver in vitro and mathematical modeling systems that are currently used in the pharmaceutical industry with an emphasis on drug metabolism, prediction of clearance, drug interaction, transporter studies and hepatotoxicity. One key message is that despite our enthusiasm for in vitro systems, we must never lose sight of the in vivo situation. Although hepatocytes have been isolated for decades, the hunt for relevant alternative systems has only just begun.

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Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME.

Gold nanorods have received much attention due to their unique optical and electronic properties which are dependent on their shape, size, and aspect ratio. This article covers in detail the synthesis, functionalization, self-assembly, and sensing applications of gold nanorods. The synthesis of three major types of rods is discussed: single-crystalline and pentahedrally-twinned rods, which are synthesized by wet chemistry methods, and polycrystalline rods, which are synthesized by templated deposition. Functionalization of these rods is usually necessary for their applications, but can often be problematic due to their surfactant coating. Thus, general strategies are provided for the covalent and noncovalent functionalization of gold nanorods. The review will then examine the significant progress that has been made in controllable assembly of nanorods into various arrangements. This assembly can have a large effect on measurable properties of rods, making it particularly applicable towards sensing of a variety of analytes. Other types of sensing not dependent on nanorod assembly, such as refractive-index based sensing, are also discussed.

Functional Gold Nanorods: Synthesis, Self-Assembly, and Sensing Applications

The article tells about the diversity of green spaces in London, the citizens’ attitude toward these spaces, and what Russian cities can learn from this experience.

Nature in London

The nanoscale control afforded by scanning probe microscopes has prompted the development of a wide variety of scanning-probe-based patterning methods. Some of these methods have demonstrated a high degree of robustness and patterning capabilities that are unmatched by other lithographic techniques. However, the limited throughput of scanning probe lithography has prevented its exploitation in technological applications. Here, we review the fundamentals of scanning probe lithography and its use in materials science and nanotechnology. We focus on robust methods, such as those based on thermal effects, chemical reactions and voltage-induced processes, that demonstrate a potential for applications.

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Advanced scanning probe lithography

Combined uptake of [18F]FDG and [18F]FMISO correlates with radiation therapy outcome in head-and-neck cancer patients.

In order to study possible toxic side effects of potential drug compounds in vitro a reliable test system is needed. Predicting liver toxicity presents a major challenge of particular importance as liver cells grown in a cell culture suffer from a rapid loss of their liver specific functions. Therefore we are developing a new microfluidic test system for liver toxicity. This test system is based on an organ-like liver 3D co-culture of hepatocytes and endothelial cells. We devised a microfluidic chip featuring cell culture chambers with integrated electrodes for the assembly of liver sinusoids by dielectrophoresis. Fluid channels enable an organ-like perfusion with culture media and test compounds. Different chamber designs were studied and optimized with regard to dielectrophoretic force distribution, hydrodynamic flow profile, and cell trapping rate using numeric simulations. Based on simulation results a microchip was injection-moulded from COP. This chip allowed the assembly of viable hepatocytes and endothelial cells in a sinusoid-like fashion.

"Artificial micro organs"--a microfluidic device for dielectrophoretic assembly of liver sinusoids.

We have used a temperature sensitive polymer film as a removable template to position, and align, gold nanorods onto an underlying target substrate. Shape-matching guiding structures for the assembly of nanorods of size 80 nm × 25 nm have been written by thermal scanning probe lithography. The nanorods were assembled into the guiding structures, which determine both the position and the orientation of single nanorods, by means of capillary interactions. Following particle assembly, the polymer was removed cleanly by thermal decomposition and the nanorods are transferred to the underlying substrate. We have thus demonstrated both the placement and orientation of nanorods with an overall positioning accuracy of ≈10 nm onto an unstructured target substrate.

Directed placement of gold nanorods using a removable template for guided assembly.

Scanning probe nanolithography (SPL) has demonstrated its potential in a variety of applications like 3D nanopatterning, 'direct development' lithography, dip-pen deposition or patterning of self-assembled monolayers. One of the main issues holding back SPL has been the limited throughput for patterning and imaging. Here we present a complete lithography and metrology system based on thermomechanical writing into organic resists. Metrology is carried out using a thermoelectric topography sensing method. More specifically, we demonstrate a system with a patterning pixel clock of 500 kHz, 20 mm s − 1 linear scan speed, a positioning accuracy of 10 nm, a read-back frequency bandwidth of 100 000 line-pairs s − 1 and a turnaround time from patterning to qualifying metrology of 1 min. Thus, we demonstrate a nanolithography system capable of implementing rapid turnaround.

https://iopscience.iop.org/article/10.1088/0957-4484/22/27/275306/pdf

Rapid turnaround scanning probe nanolithography.

Thermal scanning probe lithography is used for creating lithographic patterns with 27.5 nm half-pitch line density in a 50 nm thick high carbon content organic resist on a Si substrate. The as-written patterns in the poly phthaladehyde thermal resist layer have a depth of 8 nm, and they are transformed into high-aspect ratio binary patterns in the high carbon content resist using a SiO2 hard-mask layer with a thickness of merely 4 nm and a sequence of selective reactive ion etching steps. Using this process, a line-edge roughness after transfer of 2.7 nm (3σ) has been achieved. The patterns have also been transferred into 50 nm deep structures in the Si substrate with excellent conformal accuracy. The demonstrated process capabilities in terms of feature density and line-edge roughness are in accordance with today’s requirements for maskless lithography, for example for the fabrication of extreme ultraviolet (EUV) masks.

Felix Holzner

Papers

Combined uptake of [18F]FDG and [18F]FMISO correlates with radiation therapy outcome in head-and-neck cancer patients.

"Artificial micro organs"--a microfluidic device for dielectrophoretic assembly of liver sinusoids.

Directed placement of gold nanorods using a removable template for guided assembly.

Rapid turnaround scanning probe nanolithography.

Thermal Probe Maskless Lithography for 27.5 nm Half-Pitch Si Technology