Search

Indium Arsenide is a III-V semiconductor with low electron effective mass, a small band gap, strong spin-orbit coupling, and a large g-factor. These properties and its surface Fermi level pinned in the conduction band make InAs a good candidate for developing superconducting solid-state quantum devices. Here, we report the epitaxial growth of very thin InAs layers with thicknesses ranging from 12.5 nm to 500 nm grown by Molecular Beam Epitaxy on In x Al 1-x As metamorphic buffers. Differently than InAs substrates, these buffers have the advantage of being insulating at cryogenic temperatures, which allows for multiple device operations on the same wafer and thus making the approach scalable. The structural properties of the InAs layers were investigated by high-resolution X-ray diffraction, demonstrating the high crystal quality of the InAs layers. Furthermore, their transport properties, such as total and sheet carrier concentration, sheet resistance, and carrier mobility, were measured in the van der Pauw configuration at room temperature. A simple conduction model was employed to quantify the surface, bulk, and interface contributions to the overall carrier concentration and mobility.

The growth of high-quality graphene on flat and rigid templates, such as metal thin films on insulating wafers, is regarded as a key enabler for technologies based on 2D materials. In this work, the growth of decoupled graphene is introduced via non-reducing low-pressure chemical vapor deposition (LPCVD) on crystalline Cu(111) films deposited on sapphire. The resulting film is atomically flat, with no detectable cracks or ripples, and lies atop of a thin Cu 2 O layer, as confirmed by microscopy, diffraction, and spectroscopy analyses. Post-growth treatment of the partially decoupled graphene enables full and uniform oxidation of the interface, greatly simplifying subsequent transfer processes, particularly dry-pick up - a task that proves challenging when dealing with graphene directly synthesized on metallic Cu(111). Electrical transport measurements reveal high carrier mobility at room temperature, exceeding 10 4  cm 2  V -1  s -1 on SiO 2 /Si and 10 5  cm 2  V -1  s -1 upon encapsulation in hexagonal boron nitride (hBN). The demonstrated growth approach yields exceptional material quality, in line with micro-mechanically exfoliated graphene flakes, and thus paves the way toward large-scale production of pristine graphene suitable for high-performance next-generation applications., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Human islets of Langerhans are composed mostly of glucagon-secreting α cells and insulin-secreting β cells closely intermingled one another. Current methods for identifying α and β cells involve either fixing islets and using immunostaining or disaggregating islets and employing flow cytometry for classifying α and β cells based on their size and autofluorescence. Neither approach, however, allows investigating the dynamic behavior of α and β cells in a living and intact islet. To tackle this issue, we present a machine-learning-based strategy for identification α and β cells in label-free infrared micrographs of living human islets without immunostaining. Intrinsic autofluorescence is stimulated by infrared light and collected both in intensity and lifetime in the visible range, dominated by NAD(P)H and lipofuscin signals. Descriptive parameters are derived from micrographs for ~ 10 3 cells. These parameters are used as input for a boosted decision-tree model (XGBoost) pre-trained with immunofluorescence-derived cell-type information. The model displays an optimized-metrics performance of 0.86 (i.e. area under a ROC curve), with an associated precision of 0.94 for the recognition of β cells and 0.75 for α cells. This tool promises to enable longitudinal studies on the dynamic behavior of individual cell types at single-cell resolution within the intact tissue., (© 2024. The Author(s).)

The successful trajectory of liposome-encapsulated doxorubicin (e.g., Doxil, which has been approved by the U.S. Food and Drug Administration) as an anticancer nanodrug in clinical applications is contradicted by in vitro cell viability data that highlight its reduced efficacy in promoting cell death compared with non-encapsulated doxorubicin. No reports to date have provided a mechanistic explanation for this apparently discordant evidence. Taking advantage of doxorubicin intrinsic fluorescence and time-resolved optical microscopy, we analyze the uptake and intracellular processing of liposome-encapsulated doxorubicin (L-DOX) in several in vitro cellular models. Cell entry of L-DOX was found to lead to a rapid (seconds to minutes), energy- and temperature-independent release of crystallized doxorubicin nanorods into the cell cytoplasm, which then disassemble into a pool of fibril-shaped derivatives capable of crossing the cellular membrane while simultaneously releasing active drug monomers. Thus, a steady state is rapidly established in which the continuous supply of crystal nanorods from incoming liposomes is counteracted by a concentration-guided efflux in the extracellular medium of fibril-shaped derivatives and active drug monomers. These results demonstrate that liposome-mediated delivery is constitutively less efficient than isolated drug in establishing favorable conditions for drug retention in the cell. In addition to explaining previous contradictory evidence, present results impose careful rethinking of the synthetic identity of encapsulated anticancer drugs., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Early diagnosis is one of the most important factors in determining the prognosis in cancer. Sensitive detection and quantification of tumour-specific biomarkers have the potential to improve significantly our diagnostic capability. Here, we introduce a triggerable aptamer-based nanostructure based on an oligonucleotide/gold nanoparticle architecture that selectively disassembles in the presence of the biomarker of interest; its optimization is based also on in-silico determination of the aptamer nucleotides interactions with the protein of interest. We demonstrate this scheme for the case of Prostate Specific Membrane Antigen (PSMA) and PSMA derived from PSMA-positive exosomes. We tested the disassembly of the system by diameter and count rate measurements in dynamic light scattering, and by inspection of its plasmon resonance shift, upon addition of PSMA, finding appreciable differences down to the sub-picomolar range; this points towards the possibility that this approach may lead to sensors competitive with diagnostic biochemical assays that require enzymatic amplification. More generally, this scheme has the potential to be applied to a broad range of pathologies with specific identified biomarkers., (© 2023. The Author(s).)

Onivyde was approved by the Food and Drug Administration (FDA) in 2015 for the treatment of solid tumors, including metastatic pancreatic cancer. It is designed to encapsulate irinotecan at high concentration, increase its blood-circulation lifetime, and deliver it to cells where it is enzymatically converted into SN-38, a metabolite with 100- to 1000-fold higher anticancer activity. Despite a rewarding clinical path, little is known about the physical state of encapsulated irinotecan within Onivyde and how this synthetic identity changes throughout the process from manufacturing to intracellular processing. Herein, we exploit irinotecan intrinsic fluorescence and fluorescence lifetime imaging microscopy (FLIM) to selectively probe the supramolecular organization of the drug. FLIM analysis on the manufacturer's formulation reveals the presence of two coexisting physical states within Onivyde liposomes: (i) gelated/precipitated irinotecan and (ii) liposome-membrane-associated irinotecan, the presence of which is not inferable from the manufacturer's indications. FLIM in combination with high-performance liquid chromatography (HPLC) and a membrane-impermeable dynamic quencher of irinotecan reveals rapid (within minutes) and complete chemical dissolution of the gelated/precipitated phase upon Onivyde dilution in standard cell-culturing medium with extensive leakage of the prodrug from liposomes. Indeed, confocal imaging and cell-proliferation assays show that encapsulated and nonencapsulated irinotecan formulations are similar in terms of cell-uptake mechanism and cell-division inhibition. Finally, 2-channel FLIM analysis discriminates the signature of irinotecan from that of its red-shifted SN-38 metabolite, demonstrating the appearance of the latter as a result of Onivyde intracellular processing. The findings presented in this study offer fresh insights into the synthetic identity of Onivyde and its transformation from production to in vitro administration. Moreover, these results serve as another validation of the effectiveness of FLIM analysis in elucidating the supramolecular organization of encapsulated fluorescent drugs. This research underscores the importance of leveraging advanced imaging techniques to deepen our understanding of drug formulations and optimize their performance in delivery applications.

Background: Labeling efficiency is a crucial parameter in fluorescence applications, especially when studying biomolecular interactions. Current approaches for estimating the yield of fluorescent labeling have critical drawbacks that usually lead them to be inaccurate or not quantitative., Results: We present a method to quantify fluorescent-labeling efficiency that addresses the critical issues marring existing approaches. The method operates in the same conditions of the target experiments by exploiting a ratiometric evaluation with two fluorophores used in sequential reactions. We show the ability of the protocol to extract reliable quantification for different fluorescent probes, reagents concentrations, and reaction timing and to optimize labeling performance. As paradigm, we consider the labeling of the membrane-receptor TrkA through 4'-phosphopantetheinyl transferase Sfp in living cells, visualizing the results by TIRF microscopy. This investigation allows us to find conditions for demanding single and multi-color single-molecule studies requiring high degrees of labeling., Conclusions: The developed method allows the quantitative determination and the optimization of staining efficiency in any labeling strategy based on stable reactions., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Thermoelectric polyelectrolytes are emerging as ideal material platform for self-powered bio-compatible electronic devices and sensors. However, despite the nanoscale nature of the ionic thermodiffusion processes underlying thermoelectric efficiency boost in polyelectrolytes, to date no evidence for direct probing of ionic diffusion on its relevant length and time scale has been reported. This gap is bridged by developing heat-driven hybrid nanotransistors based on InAs nanowires embedded in thermally biased Na + -functionalized (poly)ethyleneoxide, where the semiconducting nanostructure acts as a nanoscale probe sensitive to the local arrangement of the ionic species. The impact of ionic thermoelectric gating on the nanodevice electrical response is addressed, investigating the effect of device architecture, bias configuration and frequency of the heat stimulus, and inferring optimal conditions for the heat-driven nanotransistor operation. Microscopic quantities of the polyelectrolyte such as the ionic diffusion coefficient are extracted from the analysis of hysteretic behaviors rising in the nanodevices. The reported experimental platform enables simultaneously the ionic thermodiffusion and nanoscale resolution, providing a framework for direct estimation of polyelectrolytes microscopic parameters. This may open new routes for heat-driven nanoelectronic applications and boost the rational design of next-generation polymer-based thermoelectric materials., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

The cleaning of some wooden artefacts can be challenging due to peculiar surface roughness and/or particular finishing treatments that favour the deposition of dirt and contaminants. The most common cleaning system used by conservators is agar gel, characterized by its rigidity and brittleness, which challenges the cleaning of rough and irregular surfaces typical of most wooden artefacts. In this work, alginate crosslinked with calcium (CA) and konjac glucomannan crosslinked with borax (KGB) gels were proposed to solve this issue. They were prepared and applied to smooth- and rough-surfaced mock-ups replicating wooden musical instruments' surfaces that had been subsequently covered by artificial soiling and sweat contaminants. The mechanical properties of CA and KGB gels, including their stability over a 60-day storage time, were evaluated by a texture analyzer, while cleaning efficacy was analytically evaluated by non-invasive X-ray fluorescence mapping and profilometric investigation. CA gel appeared to have a higher tensile strength and elongation at break. KGB gel was shown to be soft and resilient, indicating its suitability for cleaning rough surfaces. After repeating the cleaning application three times on the rough-surfaced mock-ups, both the CA and KGB gels were shown to have cleaning efficacy. The results obtained with CA and KGB were compared with those from the Agar application.

The supramolecular organization of Doxorubicin (DOX) within the standard Doxoves® liposomal formulation (DOX®) is investigated using visible light and phasor approach to fluorescence lifetime imaging (phasor-FLIM). First, the phasor-FLIM signature of DOX® is resolved into the contribution of three co-existing fluorescent species, each with its characteristic mono-exponential lifetime, namely: crystallized DOX (DOX c , 0.2 ns), free DOX (DOX f , 1.0 ns), and DOX bound to the liposomal membrane (DOX b , 4.5 ns). Then, the exact molar fractions of the three species are determined by combining phasor-FLIM with quantitative absorption/fluorescence spectroscopy on DOX c , DOX f , and DOX b pure standards. The final picture on DOX® comprises most of the drug in the crystallized form (∼98%), with the remaining fractions divided between free (∼1.4%) and membrane-bound drug (∼0.7%). Finally, phasor-FLIM in the presence of a DOX dynamic quencher allows us to suggest that DOX f is both encapsulated and non-encapsulated, and that DOX b is present on both liposome-membrane leaflets. We argue that the present experimental protocol can be applied to the investigation of the supramolecular organization of encapsulated luminescent drugs/molecules all the way from the production phase to their state within living matter.

InSb nanoflags are grown by chemical beam epitaxy in regular arrays on top of Au-catalyzed InP nanowires synthesized on patterned SiO 2 /InP(111)B substrates. Two-dimensional geometry of the nanoflags is achieved by stopping the substrate rotation in the step of the InSb growth. Evolution of the nanoflag length, thickness and width with the growth time is studied for different pitches (distances in one of the two directions of the substrate plane). A model is presented which explains the observed non-linear time dependence of the nanoflag length, saturation of their thickness and gradual increase in the width by the shadowing effect for re-emitted Sb flux. These results might be useful for morphological control of InSb and other III-V nanoflags grown in regular arrays.