Artificial Channels in an Infectious Biofilm Created by Magnetic Nanoparticles Enhanced Bacterial Killing by Antibiotics

The poor penetrability of many biofilms contributes to the recalcitrance of infectious biofilms to antimicrobial treatment. Here, a new application for the use of magnetic nanoparticles in nanomedicine to create artificial channels in infectious biofilms to enhance antimicrobial penetration and bacterial killing is proposed. Staphylococcus aureus biofilms are exposed to magnetic‐iron‐oxide nanoparticles (MIONPs), while magnetically forcing MIONP movement through the biofilm. Confocal laser scanning microscopy demonstrates artificial channel digging perpendicular to the substratum surface. Artificial channel digging significantly (4–6‐fold) enhances biofilm penetration and bacterial killing efficacy by gentamicin in two S. aureus strains with and without the ability to produce extracellular polymeric substances. Herewith, this work provides a simple, new, and easy way to enhance the eradication of infectious biofilms using MIONPs combined with clinically applied antibiotic therapies.     

Eradication of Multidrug‐Resistant Staphylococcal Infections by Light‐Activatable Micellar Nanocarriers in a Murine Model

Bacterial infections are mostly due to bacteria in their biofilm mode‐of‐growth, making them recalcitrant to antibiotic penetration. In addition, the number of bacterial strains intrinsically resistant to available antibiotics is alarmingly growing. This study reports that micellar nanocarriers with a poly(ethylene glycol) shell fully penetrate staphylococcal biofilms due to their biological invisibility. However, when the shell is complemented with poly(β‐amino ester), these mixed‐shell micelles become positively charged in the low pH environment of a biofilm, allowing not only their penetration but also their accumulation in biofilms without being washed out, as do single‐shell micelles lacking the pH‐adaptive feature. Accordingly, bacterial killing of multidrug resistant staphylococcal biofilms exposed to protoporphyrin IX‐loaded mixed‐shell micelles and after light‐activation is superior compared with single‐shell micelles. Subcutaneous infections in mice, induced with vancomycin‐resistant, bioluminescent staphylococci can be eradicated by daily injection of photoactivatable protoporphyrin IX‐loaded, mixed‐shell micelles in the bloodstream and light‐activation at the infected site. Micelles, which are not degraded by bacterial enzymes in the biofilm, are degraded in the liver and spleen and cleared from the body through the kidneys. Thus, adaptive micellar nanocarriers loaded with light‐activatable antimicrobials constitute a much‐needed alternative to current antibiotic therapies.     

Fabrication and characterization of nanopore-based electrodes with radii down to 2 nm

We report on the fabrication and characterization of gold nanoelectrodes with carefully controlled nanometer dimensions in a matrix of insulating silicon nitride. A focused electron beam was employed to drill nanopores in a thin silicon nitride membrane. The size and shape of the nanopores were studied with high-resolution transmission electron microscopy and electron-energy-loss two-dimensional maps. The pores were subsequently filled with gold, yielding conically shaped nanoelectrodes. The nanoelectrodes were examined by atomic and electrostatic force microscopy. Their applicability in electrochemistry was demonstrated by steady-state cyclic voltammetry. Pores with a radii down to 0.4 nm and electrodes with radii down to 2 nm are demonstrated.     

Atomic-scale electron-beam sculpting of near-defect-free graphene nanostructures

In order to harvest the many promising properties of graphene in (electronic) applications, a technique is required to cut, shape, or sculpt the material on the nanoscale without inducing damage to its atomic structure, as this drastically influences the electronic properties of the nanostructure. Here, we reveal a temperature-dependent self-repair mechanism that allows near-damage-free atomic-scale sculpting of graphene using a focused electron beam. We demonstrate that by sculpting at temperatures above 600 °C, an intrinsic self-repair mechanism keeps the graphene in a single-crystalline state during cutting, even though the electron beam induces considerable damage. Self-repair is mediated by mobile carbon ad-atoms that constantly repair the defects caused by the electron beam. Our technique allows reproducible fabrication and simultaneous imaging of single-crystalline free-standing nanoribbons, nanotubes, nanopores, and single carbon chains.     

The Impact of Kilning on Enzymatic Activity of Buckwheat Malt

This study investigated the impact of kilning on α‐amylase, β‐amylase (total and soluble), β‐glucanase and protease activities in buckwheat malt. Common buckwheat (Fagopyrum esculentum) was steeped at 10°C for 12 h, germinated at 15°C for 4 days and kilned at 40°C for 48 h. Moisture content and enzymatic activities were determined throughout the kilning period. Results showed moisture content was reduced from 44% to 5% after 48 h of kilning at 40°C. β‐Amylase was found to exist in a soluble and latent form in buckwheat. Maximum activity of (a) α‐amylase, (b) total β‐amylase, (c) soluble β‐amylase, (d) β‐glucanase and (e) protease activity occurred after (a) 8, (b) 7, (c) 30, (d) 0, and (e) 8 h of kilning, respectively. The final malt exhibited very little β‐glucanase and cellulase activity. Proteolytic activity was low in buckwheat malt when compared to the barley malt control. All enzymatic activities were found to decrease during the kilning stage. Results indicated that after prolonged kilning at 40°C, inactivation of hydrolytic enzymes occurred; two‐stage kilning for shorter periods is recommended. Although, amylolytic activity was low in malted buckwheat, buckwheat malt shows potential as an ingredient for the brewing and cereal industry.     

Does individual or collaborative self-debriefing better enhance learning from games?

The primary aim of this study is to find out whether use of different self-debriefing modes affects learning from a game. In self-debriefing participants are led to reflect upon their game experiences by a set of debriefing questions. Two conditions were compared: Individual and Collaborative self-debriefing. The 45 participants first played the game of Lemonade Tycoon Deluxe, were tested for knowledge and self-debriefed in pairs or alone. Then they played the game once more and were tested again. Game scores increased significantly from the first to the second round of gameplay to an equal degree in both conditions. Knowledge scores of participants in individual self-debriefing increased significantly more than those of participants in the Collaborative condition. The study shows that game-based learning can be effectively scaffolded with self-debriefing. Future studies might investigate whether the type of self-debriefing differentially affects game motivation. In addition, attention to the role of feedback is called for.     

Length‐Scale Mediated Differential Adhesion of Mammalian Cells and Microbes

Surfaces of implantable biomedical devices are increasingly engineered to promote their interactions with tissue. However, surfaces that stimulate desirable mammalian cell adhesion, spreading, and proliferation also enable microbial colonization. The biomaterials‐associated infection that can result is now a critical clinical problem. We have identified an important mechanism to create a surface that can simultaneously promote healing while reducing the probability of infection. Surfaces are created with submicrometer‐sized, non‐adhesive microgels patterned on an otherwise cell‐adhesive surface. Quantitative force measurements between a staphylococcus and a patterned surface show that the adhesion strength decreases significantly at inter‐gel spacings comparable to bacterial dimensions. Time‐resolved flow‐chamber measurements show that the microbial deposition rate dramatically decreases at these same spacings. Importantly, the adhesion and spreading of osteoblast‐like cells is preserved despite the sub‐cellular non‐adhesive surface features. Since such length‐scale‐mediated differential interactions do not rely on antibiotics, this mechanism can be particularly significant in mitigating biomaterials‐associated infection by antibiotic‐resistant bacteria such as MRSA.     

Air gap formation by UV-assisted decomposition of CVD material

A sacrificial material deposited by CVD is used to demonstrate air gap formation in single damascene structures by UV-assisted decomposition. The material is removed through a porous low-k cap, after completion of the damascene scheme. The porosity of the low-k cap is shown to be critical for efficient air gap formation. Capacitance reduction of ∼50% is demonstrated using this technique compared to conventional SiOC(H) interconnects and an effective dielectric constant of 1.7 is extrapolated.     

Probing colloid-substratum contact stiffness by acoustic sensing in a liquid phase

In a quartz crystal microbalance, particles adhering to a sensor crystal are perturbed around their equilibrium positions via thickness-shear vibrations at the crystal's fundamental frequency and overtones. The amount of adsorbed molecular mass is measured as a shift in resonance frequency. In inertial loading, frequency shifts are negative and proportional to the adsorbed mass, in contrast with "elastic loading", where particles adhere via small contact points. Elastic loading in air yields positive frequency shifts according to a coupled resonance model. We explore here the novel application of a coupled resonance model for colloidal particle adhesion in a liquid phase theoretically and demonstrate its applicability experimentally. Particles with different radii and in the absence and presence of ligand-receptor binding showed evidence of coupled resonance. By plotting the frequency shifts versus the quartz crystal microbalance with dissipation overtone number, frequencies of zero-crossing could be inferred, indicative of adhesive bond stiffness. As a novelty of the model, it points to a circular relation between bandwidth versus frequency shift, with radii indicative of bond stiffness. The model indicates that bond stiffness for bare silica particles adhering on a crystal surface is determined by attractive Lifshitz-van der Waals and ionic-strength-dependent, repulsive electrostatic forces. In the presence of ligand-receptor interactions, softer interfaces develop that yield stiffer bonds due to increased contact areas. In analogy with molecular vibrations, the radii of adhering particles strongly affect the resonance frequencies, while bond stiffness depends on environmental parameters to a larger degree than for molecular adsorption.