Coherent Fiber-Optic Sensor for Ultra-Acoustic Crack Emissions.

A coherent optical fiber sensor with adequate sensitivity for detecting the acoustic emission (AE) during the propagation of a crack in a ferrous material is presented. The proposed fiber optic sensor is successfully compared in terms of the SNR (Signal to Noise Ratio) and detectable AE energy levels to commercially available AE piezo-transducers sensors and is proven to be an effective and advantageous alternative for sensing and monitoring fatigue damage in structural applications.

Fast and Purification-Free Characterization of Bio-Nanoparticles in Biological Media by Electrical Asymmetrical Flow Field-Flow Fractionation Hyphenated with Multi-Angle Light Scattering and Nanoparticle Tracking Analysis Detection.

Accurate physico-chemical characterization of exosomes and liposomes in biological media is challenging due to the inherent complexity of the sample matrix. An appropriate purification step can significantly reduce matrix interferences, and thus facilitate analysis of such demanding samples. Electrical Asymmetrical Flow Field-Flow Fractionation (EAF4) provides online sample purification while simultaneously enabling access to size and Zeta potential of sample constituents in the size range of approx. 1-1000 nm. Hyphenation of EAF4 with Multi-Angle Light Scattering (MALS) and Nanoparticle Tracking Analysis (NTA) detection adds high resolution size and number concentration information turning this setup into a powerful analytical platform for the comprehensive physico-chemical characterization of such challenging samples. We here present EAF4-MALS hyphenated with NTA for the analysis of liposomes and exosomes in complex, biological media. Coupling of the two systems was realized using a flow splitter to deliver the sample at an appropriate flow speed for the NTA measurement. After a proof-of-concept study using polystyrene nanoparticles, the combined setup was successfully applied to analyze liposomes and exosomes spiked into cell culture medium and rabbit serum, respectively. Obtained results highlight the benefits of the EAF4-MALS-NTA platform to study the behavior of these promising drug delivery vesicles under in vivo like conditions.

Static Behavior of a 3D-Printed Short Carbon Fiber Polyamide: Influence of the Meso-Structure and Water Content.

The knowledge of the mechanical behavior of a 3D-printed material is fundamental for the 3D printing outbreaking technology to be considered for a range of applications. In this framework, the significance, reliability, and accuracy of the information obtained by testing material coupons assumes a pivotal role. The present work focuses on an evaluation of the static mechanical properties and failure modes of a 3D-printed short carbon fiber-reinforced polyamide in relation to the specimen's unique meso-structural morphology and water content. Within the manufacturing limitations of a commercially available printer, specimens of dedicated combinations of geometry and printing patterns were specifically conceived and tested. The specimens' meso-structure morphologies were investigated by micro-computed tomography. The material failure mechanisms were inferred from an analysis of the specimens' fracture surfaces and failure morphologies. The outcomes of the present analysis indicate that each test specimen retained proper mechanical properties, thereby suggesting that they should be accurately designed to deliver representative information of the underlying material beads or of their deposition layout. Suggestions on the adoption of preferred test specimens for evaluating specific material properties were proposed.

Quality assessment of LNP-RNA therapeutics with orthogonal analytical techniques.

The availability of analytical methods for the characterization of lipid nanoparticles (LNPs) for in-vivo intracellular delivery of nucleic acids is critical for the fast development of innovative RNA therapies. In this study, analytical protocols to measure (i) chemical composition, (ii) drug loading, (iii) particle size, concentration, and stability as well as (iv) structure and morphology were evaluated and compared based on a comprehensive characterization strategy linking key physical and chemical properties to in-vitro efficacy and toxicity. Furthermore, the measurement protocols were assessed either by testing the reproducibility and robustness of the same technique in different laboratories, or by a correlative approach, comparing measurement results of the same attribute with orthogonal techniques. The characterization strategy and the analytical measurements described here will have an important role during formulation development and in determining robust quality attributes ultimately supporting the quality assessment of these innovative RNA therapeutics.

Nanoparticle Tracking Analysis of Gold Nanoparticles in Aqueous Media through an Inter-Laboratory Comparison.

In the field of nanotechnology, analytical characterization plays a vital role in understanding the behavior and toxicity of nanomaterials (NMs). Characterization needs to be thorough and the technique chosen should be well-suited to the property to be determined, the material being analyzed and the medium in which it is present. Furthermore, the instrument operation and methodology need to be well-developed and clearly understood by the user to avoid data collection errors. Any discrepancies in the applied method or procedure can lead to differences and poor reproducibility of obtained data. This paper aims to clarify the method to measure the hydrodynamic diameter of gold nanoparticles by means of Nanoparticle Tracking Analysis (NTA). This study was carried out as an inter-laboratory comparison (ILC) amongst seven different laboratories to validate the standard operating procedure's performance and reproducibility. The results obtained from this ILC study reveal the importance and benefits of detailed standard operating procedures (SOPs), best practice updates, user knowledge, and measurement automation.

Not only Alagille syndrome. Syndromic paucity of interlobular bile ducts secondary to HNF1ß deficiency: a case report and literature review.

BACKGROUND: paucity of interlobular bile ducts is an important observation at liver biopsy in the diagnostic work-up of neonatal cholestasis. To date, other than in the Alagille syndrome, syndromic paucity of interlobular bile ducts has been documented in four cholestatic neonates with HFN1ß mutations. A syndromic phenotype, known as renal cysts and diabetes syndrome (RCAD), has been identified. This is usually characterized by a wide clinical spectrum, including renal cysts, maturity-onset diabetes of the young, exocrine pancreatic insufficiency, urogenital abnormalities and a not well established liver involvement. Herein we report a novel case of paucity of interlobular bile ducts due to an HFN1ß defect. CASE PRESENTATION: A 5-week-old boy was admitted to our department for cholestatic jaundice with increased gamma-glutamyl transpeptidase and an unremarkable clinical examination. He had been delivered by Caesarian section at 38 weeks' gestation from unrelated parents, with a birth weight of 2600 g (3rd percentile). Screening for cholestatic diseases, including Alagille syndrome, was negative except for a minor pulmonary artery stenosis at echocardiography and a doubt of a thoracic butterfly hemivertebra. The finding of hyperechogenic kidneys with multiple bilateral cortical cysts at ultrasound examination, associated with moderately impaired renal function with proteinuria, polyuria and metabolic acidosis, was suggestive of ciliopathy. A liver biopsy was performed revealing paucity of interlobular bile ducts, thus the diagnosis of Alagille syndrome was reconsidered. Although genetic tests for liver cholestatic diseases were performed with negative results for Alagille syndrome (JAG1 and NOTCH2), a de-novo missense mutation of HNF1ß gene was detected. At 18 months of age our patient has persistent cholestasis and his itching is not under satisfactory control. CONCLUSIONS: Alagille syndrome may not be the only syndrome determining paucity of interlobular bile ducts in neonates presenting with cholestasis and renal impairment, especially in small for gestational age newborns. We suggest that HNF1ß deficiency should also be ruled out, taking into consideration HNF1ß mutations, together with Alagille syndrome, in next generation sequencing strategies in neonates with cholestasis, renal impairment and/or paucity of interlobular bile ducts at liver biopsy.

A Lamb waves based statistical approach to structural health monitoring of carbon fibre reinforced polymer composites.

This research investigates a Lamb-wave based structural health monitoring approach matching an out-of-phase actuation of a pair of piezoceramic transducers at low frequency. The target is a typical quasi-isotropic carbon fibre reinforced polymer aeronautical laminate subjected to artificial, via Teflon patches, and natural, via suitable low velocity drop weight impact tests, delaminations. The performance and main influencing factors of such an approach are studied through a Design of Experiment statistical method, considering both Pulse Echo and Pitch Catch configurations of PZT sensors. Results show that some factors and their interactions can effectively influence the detection of a delamination-like damage.

Spatiotemporal dynamics of doxorubicin elution from embolic beads within a microfluidic network.

Anticancer treatment using embolic drug-eluting beads (DEBs) has shown multifarious advantages compared to systemic chemotherapy. However, there is a growing need for a better understanding of the physical parameters governing drug-elution from embolic devices under physiologically relevant fluidic conditions. In the present study, we investigated the spatiotemporal dynamics of doxorubicin hydrochloride elution from drug-loaded hydrogel embolic beads within a microfluidic device consisting of a network of interconnected microchannels which replicates the architectural properties of microvascular systems. Drug-elution has been investigated experimentally at a single-bead level, using in-house developed microscopy- and spectrofluorimetry-based methods. Results demonstrated that the kinetics of drug-elution and the amount of eluted drug strongly depended on the location of the embolic event within the embolised channel (e.g. fractional amount of eluted drug after 3h was equal to ~0.2 and ~0.6 for completely-confined and partially-confined bead, respectively). Drug-elution from partially-confined bead showed a counterintuitive dependence on the local Reynolds number (and thus on the mean fluid velocity), as a result of dynamic changes in bead compressibility causing the displacement of the bead from the primary embolic site. Conversely, the kinetics of drug-elution from fully-confined bead was less affected by the local Reynolds number and bead displayed faster elution from the surface area exposed to the systemic flow, which was associated with the formation of fluid eddies nearby the bead post embolisation.

A thin-reflector microfluidic resonator for continuous-flow concentration of microorganisms: a new approach to water quality analysis using acoustofluidics.

An acoustofluidic device has been developed for concentrating vegetative bacteria in a continuous-flow format. We show that it is possible to overcome the disruptive effects of acoustic streaming which typically dominate for small target particles, and demonstrate flow rates compatible with the testing of drinking water. The device consists of a thin-reflector multi-layered resonator, in which bacteria in suspension are levitated towards a glass surface under the action of acoustic radiation forces. In order to achieve robust device performance over long-term operation, functional tests have been carried out to (i) maintain device integrity over time and stabilise its resonance frequency, (ii) optimise the operational acoustic parameters, and (iii) minimise bacterial adhesion on the inner surfaces. Using the developed device, a significant increase in bacterial concentration has been achieved, up to a maximum of ~60-fold. The concentration performance of thin-reflector resonators was found to be superior to comparable half-wave resonators.