Andreev Molecule in Parallel InAs Nanowires.

Coupling individual atoms fundamentally changes the state of matter: electrons bound to atomic cores become delocalized turning an insulating state to a metallic one. A chain of atoms could lead to more exotic states if the tunneling takes place via the superconducting vacuum and can induce topologically protected excitations like Majorana or parafermions. Although coupling a single atom to a superconductor is well studied, the hybridization of two sites with individual tunability was not reported yet. The peculiar vacuum of the Bardeen-Cooper-Schrieffer (BCS) condensate opens the way to annihilate or generate two electrons from the bulk resulting in a so-called Andreev molecular state. By employing parallel nanowires with an Al shell, two artificial atoms were created at a minimal distance with an epitaxial superconducting link between. Hybridization via the BCS vacuum was observed and the spectrum of an Andreev molecule as a function of level positions was explored for the first time.

Gate-Controlled Supercurrent in Epitaxial Al/InAs Nanowires.

Gate-controlled supercurrent (GCS) in superconducting nanobridges has recently attracted attention as a means to create superconducting switches. Despite the clear advantages for applications, the microscopic mechanism of this effect is still under debate. In this work, we realize GCS for the first time in a highly crystalline superconductor epitaxially grown on an InAs nanowire. We show that the supercurrent in the epitaxial Al layer can be switched to the normal state by applying ≃±23 V on a bottom gate insulated from the nanowire by a crystalline hBN layer. Our extensive study of the temperature and magnetic field dependencies suggests that the electric field is unlikely to be the origin of GCS in our device. Though hot electron injection alone cannot explain our experimental findings, a very recent non-equilibrium phonons based picture is compatible with most of our results.

Highly symmetric and tunable tunnel couplings in InAs/InP nanowire heterostructure quantum dots.

We present a comprehensive electrical characterization of an InAs/InP nanowire (NW) heterostructure, comprising of two InP barriers forming a quantum dot (QD), two adjacent lead segments and two metallic contacts. We demonstrate how to extract valuable quantitative information of the QD. The QD shows very regular Coulomb blockade resonances over a large gate voltage range. By analyzing the resonance line shapes, we map the evolution of the tunnel couplings from the few to the many electron regime, with electrically tunable tunnel couplings from <1 µeV to >600 µeV, and a transition from the temperature to the lifetime broadened regime. The InP segments form tunnel barriers with almost fully symmetric tunnel couplings and a barrier height of ∼350 meV. All of these findings can be understood in great detail based on the deterministic material composition and geometry. Our results demonstrate that integrated InAs/InP QDs provide a promising platform for electron tunneling spectroscopy in InAs NWs, which can readily be contacted by a variety of superconducting materials to investigate subgap states in proximitized NW regions, or be used to characterize thermoelectric nanoscale devices in the quantum regime.

Effects of omitting titanium dioxide from the film coating of a pharmaceutical tablet - An industrial case study of attempting to comply with EU regulation 2022/63.

Recently, concerns have been raised about the safety of titanium dioxide (TiO2), a commonly used component of pharmaceutical film coatings. The European Union has recently prohibited the application of this material in the food industry, and it is anticipated that the same will happen in the pharmaceutical industry. For this reason, pharmaceutical manufacturers have to consider the possible impact of removing TiO2 from the film coating of tablets. In this paper, we present a case study of a commercially produced tablet where the film coating containing TiO2 was replaced with a coating using calcium carbonate (CaCO3) or with a transparent coating. The performance of the coatings was compared by measuring the moisture absorption rate and the dissolution profile of the tablets. In these regards, there were negligible differences between the coating types. The tablets contained a highly photosensitive drug, the ability of the coatings to protect the drug was evaluated through environmental stability and photostability measurements. The HPLC results showed that the inclusion of TiO2 does not provide additional benefits, when humidity and thermal stress is applied, however its role was vital in protecting the drug from external light. There were several decomposition products which appeared in large quantities when TiO2 was missing from the coating. These results imply that photosensitivity is an issue, replacing TiO2 will be challenging, though its absence can be tolerated when the drug does not need to be protected from light.

Signatures of Gate-Driven Out-of-Equilibrium Superconductivity in Ta/InAs Nanowires.

Understanding the microscopic origin of the gate-controlled supercurrent (GCS) in superconducting nanobridges is crucial for engineering superconducting switches suitable for a variety of electronic applications. The origin of GCS is controversial, and various mechanisms have been proposed to explain it. In this work, we have investigated the GCS in a Ta layer deposited on the surface of InAs nanowires. Comparison between switching current distributions at opposite gate polarities and between the gate dependence of two opposite side gates with different nanowire-gate spacings shows that the GCS is determined by the power dissipated by the gate leakage. We also found a substantial difference between the influence of the gate and elevated bath temperature on the magnetic field dependence of the supercurrent. Detailed analysis of the switching dynamics at high gate voltages shows that the device is driven into the multiple phase slips regime by high-energy fluctuations arising from the leakage current.

Interpretable artificial neural networks for retrospective QbD of pharmaceutical tablet manufacturing based on a pilot-scale developmental dataset.

As the pharmaceutical industry increasingly adopts the Pharma 4.0. concept, there is a growing need to effectively predict the product quality based on manufacturing or in-process data. Although artificial neural networks (ANNs) have emerged as powerful tools in data-rich environments, their implementation in pharmaceutical manufacturing is hindered by their black-box nature. In this work, ANNs were developed and interpreted to demonstrate their applicability to increase process understanding by retrospective analysis of developmental or manufacturing data. The in vitro dissolution and hardness of extended-release, directly compressed tablets were predicted from manufacturing and spectroscopic data of pilot-scale development. The ANNs using material attributes and operational parameters provided better results than using NIR or Raman spectra as predictors. ANNs were interpreted by sensitivity analysis, helping to identify the root cause of the batch-to-batch variability, e.g., the variability in particle size, grade, or substitution of the hydroxypropyl methylcellulose excipient. An ANN-based control strategy was also successfully utilized to mitigate the batch-to-batch variability by flexibly operating the tableting process. The presented methodology can be adapted to arbitrary data-rich manufacturing steps from active substance synthesis to formulation to predict the quality from manufacturing or development data and gain process understanding and consistent product quality.

Large spatial extension of the zero-energy Yu-Shiba-Rusinov state in a magnetic field.

Various promising qubit concepts have been put forward recently based on engineered superconductor subgap states like Andreev bound states, Majorana zero modes or the Yu-Shiba-Rusinov (Shiba) states. The coupling of these subgap states via a superconductor strongly depends on their spatial extension and is an essential next step for future quantum technologies. Here we investigate the spatial extension of a Shiba state in a semiconductor quantum dot coupled to a superconductor. With detailed transport measurements and numerical renormalization group calculations we find a remarkable more than 50 nm extension of the zero energy Shiba state, much larger than the one observed in very recent scanning tunneling microscopy measurements. Moreover, we demonstrate that its spatial extension increases substantially in a magnetic field.

Videometric mass flow control: A new method for real-time measurement and feedback control of powder micro-feeding based on image analysis.

The present paper reports the first monitoring and control of ultra-low dose powder feeding using a camera image-based mass flow measurement system. Caffeine was fed via a single-screw microfeeder as a model active pharmaceutical ingredient (API). The mass, mass flow and sizes of the particles were successfully monitored in real-time by the developed videometric system consisting of a high-speed process camera coupled with an image analysis software. The system was also tested in feedback control mode to automatically reach the desired mass flow values by adjusting the feeder speed based on the mass flow measured by the image analysis system. Based on these features, the developed videometric system can serve as a multi-purpose PAT-tool and can provide valuable real-time information about the process which is indispensable for modern continuous pharmaceutical manufacturing.

Determination of the Membrane Environment of CD59 in Living Cells.

The organization and dynamics of proteins and lipids in the plasma membrane, and their role in membrane functionality, have been subject of a long-lasting debate. Specifically, it is unclear to what extent membrane proteins are affected by their immediate lipid environment and vice versa. Studies on model membranes and plasma membrane vesicles indicated preferences of proteins for lipid phases characterized by different acyl chain order; however, whether such phases do indeed exist in live cells is still not known. Here, we refine a previously developed micropatterning approach combined with single molecule tracking to quantify the influence of the glycosylphosphatidylinositol-anchored (GPI-anchored) protein CD59 on its molecular environment directly in the live cell plasma membrane. We find that locally enriched and immobilized CD59 presents obstacles to the diffusion of fluorescently labeled lipids with a different phase-partitioning behavior independent of cell cholesterol levels and type of lipid. Our results give no evidence for either specific binding of the lipids to CD59 or the existence of nanoscopic ordered membrane regions associated with CD59.

Homogenization of Amorphous Solid Dispersions Prepared by Electrospinning in Low-Dose Tablet Formulation.

Low-dose tablet formulations were produced with excellent homogeneity based on drug-loaded electrospun fibers prepared by single-needle as well as scaled-up electrospinning (SNES and HSES). Carvedilol (CAR), a BCS II class compound, served as the model drug while poly (vinylpyrrolidone-co-vinyl acetate) (PVPVA64) was adopted as the fiber-forming polymer. Scanning electron microscopy (SEM) imaging was used to study the morphology of HSES and SNES samples. Different homogenization techniques were compared to maximize homogeneity: mixing in plastic bags and in a high-shear granulator resulting in low-shear mixing (LSM) and high-shear mixing (HSM). Drug content and homogeneity of the tablets were measured by UV-Vis spectrometry, the results revealed acceptably low-dose fluctuations especially with formulations homogenized with HSM. Sieve analysis was used on the final LSM and HSM powder mixtures in order to elucidate the observed differences between tablet homogeneity. Tablets containing drug-loaded electrospun fibers were also studied by Raman mapping demonstrating evenly distributed CAR within the corpus.

A Fast and Simple Contact Printing Approach to Generate 2D Protein Nanopatterns.

Protein micropatterning has become an important tool for many biomedical applications as well as in academic research. Current techniques that allow to reduce the feature size of patterns below 1 µm are, however, often costly and require sophisticated equipment. We present here a straightforward and convenient method to generate highly condensed nanopatterns of proteins without the need for clean room facilities or expensive equipment. Our approach is based on nanocontact printing and allows for the fabrication of protein patterns with feature sizes of 80 nm and periodicities down to 140 nm. This was made possible by the use of the material X-poly(dimethylsiloxane) (X-PDMS) in a two-layer stamp layout for protein printing. In a proof of principle, different proteins at various scales were printed and the pattern quality was evaluated by atomic force microscopy (AFM) and super-resolution fluorescence microscopy.

Interactions of Bacterial Lipopolysaccharides with Gold Nanorod Surfaces Investigated by Refractometric Sensing.

The interface between nanoparticles and bacterial surfaces is of great interest for applications in nanomedicine and food safety. Here, we demonstrate that interactions between gold nanorods and bacterial surface molecules are governed by the nanoparticle surface coating. Polymer-coated gold nanorod substrates are exposed to lipopolysaccharides extracted from Pseudomonas aeruginosa, Salmonella enterica and Escherichia coli, and attachment is monitored using localized surface plasmon resonance refractometric sensing. The number of lipopolysaccharide molecules attached per nanorod is calculated from the shift in the plasmon maximum, which results from the change in refractive index after analyte binding. Colloidal gold nanorods in water are also incubated with lipopolysaccharides to demonstrate the effect of lipopolysaccharide concentration on plasmon shift, ζ-potential, and association constant. Both gold nanorod surface charge and surface chemistry affect gold nanorod-lipopolysaccharide interactions. In general, anionic lipopolysaccharides was found to attach more effectively to cationic gold nanorods than to neutral or anionic gold nanorods. Some variation in lipopolysaccharide attachment is also observed between the three strains studied, demonstrating the potential complexity of bacteria-nanoparticle interactions.

Evaluation of a novel magneto-optical method for the detection of malaria parasites.

Improving the efficiency of malaria diagnosis is one of the main goals of current malaria research. We have recently developed a magneto-optical (MO) method which allows high-sensitivity detection of malaria pigment (hemozoin crystals) in blood via the magnetically induced rotational motion of the hemozoin crystals. Here, we evaluate this MO technique for the detection of Plasmodium falciparum in infected erythrocytes using in-vitro parasite cultures covering the entire intraerythrocytic life cycle. Our novel method detected parasite densities as low as ∼ 40 parasites per microliter of blood (0.0008% parasitemia) at the ring stage and less than 10 parasites/µL (0.0002% parasitemia) in the case of the later stages. These limits of detection, corresponding to approximately 20 pg/µL of hemozoin produced by the parasites, exceed that of rapid diagnostic tests and compete with the threshold achievable by light microscopic observation of blood smears. The MO diagnosis requires no special training of the operator or specific reagents for parasite detection, except for an inexpensive lysis solution to release intracellular hemozoin. The devices can be designed to a portable format for clinical and in-field tests. Besides testing its diagnostic performance, we also applied the MO technique to investigate the change in hemozoin concentration during parasite maturation. Our preliminary data indicate that this method may offer an efficient tool to determine the amount of hemozoin produced by the different parasite stages in synchronized cultures. Hence, it could eventually be used for testing the susceptibility of parasites to antimalarial drugs.