The combination of complementary techniques for materials analysis can play a key role in both art conservation and academic research. Nowadays, the correlation of x-ray fluorescence (XRF) with hyperspectral reflectance imaging in the visible and infrared region has become a valuable tool for palette identification, painting techniques studies and for the diagnostic support dedicated to restoration and conservation. Moreover, both techniques enable researchers to reveal fascinating underpaintings, "pentimenti", or even preparatory drawings offering new details on the creative process of the artist. This background has been a strong motivation for the development of a new multimodal tool for art and conservation: IRIS. IRIS is a mobile and reconfigurable scanner designed to address a wide range of demanding application, exploiting the opportunities given by simultaneous MA-XRF and hyperspectral reflectance scanning in the visible-near-infrared (VNIR) and short-wave-infrared (SWIR) range from 400 to 2500 nm. The system has been designed for in-situ, fast and non-invasive scanning of the sample without compromising spectral resolution and high throughput performance. The scanner acquires co-registered XRF/VNIR-SWIR data, thus allowing the user to obtain the maximum profit from their possible correlated information: the two techniques can provide enhanced or complementary information on the same spot of analysis with minimum effort in terms of data processing and no need for spatial alignment. In the present work, the qualitative and quantitative performance of IRIS are explored, together with the presentation of in-lab analysis on reference samples and a brief insight on a real case-study.

BACKGROUND:Based on the volume of tissue removed, conservative surgery (BCS) cannot always guarantee satisfactory cosmetic results, unless resorting to more complex oncoplastic approaches. Investigating an alternative to optimize aesthetic outcomes minimizing surgical complexity, was the purpose of this study. We assessed an innovative surgical procedure based on the use of a biomimetic polyurethane-based scaffold intended for regenerating soft-tissue resembling fat, in patients undergoing BCS for non-malignant breast lesions. Safety and performance of the scaffold, and safety and feasibility of the entire implant procedure were evaluated.METHODS:A volunteer sample of 15 female patients underwent lumpectomy with immediate device positioning, performing seven study visits with six-month follow-up. We evaluated incidence of adverse events (AEs), changes in breast appearance (using photographs and anthropomorphic measurements), interference with ultrasound and MRI (assessed by two independent investigators), investigator's satisfaction (through a VAS scale), patient's pain (through a VAS scale) and quality of life (QoL) (using the BREAST-Q© questionnaire). Data reported are the results of the interim analysis on the first 5 patients.RESULTS:No AEs were device related nor serious. Breast appearance was unaltered and the device did not interference with imaging. High investigator's satisfaction, minimal post-operative pain and positive impact on QoL were also detected.CONCLUSIONS:Albeit on a limited number of patients, data showed positive outcomes both in terms of safety and performance, paving the way to an innovative breast reconstructive approach with a potential remarkable impact on clinical application of tissue engineering.TRIAL REGISTRATION:ClinicalTrials.gov (NCT04131972, October 18, 2019).

The new challenge in the investigation of cultural heritage is the possibility to obtain stratigraphical information about the distribution of the different organic and inorganic components without sampling. In this paper recently commercialized analytical set-up, which is able to co-register VNIR, SWIR, and XRF spectral data simultaneously, is exploited in combination with an innovative multivariate and multiblock high-throughput data processing for the analysis of multilayered paintings. The instrument allows to obtain elemental and molecular information from superficial to subsurface layers across the investigated area. The chemometric strategy proved to be highly efficient in data reduction and for the extraction and integration of the most useful information coming from the three different spectroscopies, also filling the gap between data acquisition and data understanding through the combination of principal component analysis (PCA), brushing, correlation diagrams and maps (within and between spectral blocks) on the low-level fused. In particular, correlation diagrams and maps provide useful information for the reconstruction of a stratigraphic structure without the need to take any sample, thanks to the effective account for inter-correlation among data (variables), which is able to effectively characterize the possible combinations of components located in the same depth level. The highly innovative technology and the data processing strategy are applied for the multi-level characterization of a complex painting reproduction as an illustrative pilot study.

DANTE is a new Digital Pulse Processor (DPP) developed for fluorescence detectors, like Silicon Drift Detectors (SDDs) or High Purity Germanium detectors (HPGe), used in X-ray Fluorescence (XRF) and X-ray Absorption Spectroscopy (XAS) experiments at synchrotron facilities. Its main features are its optimal energy resolution and peak stability for detector count rate values up to 1-2 Mcps, and its enhanced rejection of pile-up events. In this paper, we present the first complete evaluation of DANTE performance in SOLEIL synchrotron facility. DANTE has been tested in laboratory with an X-ray generator source and in different experiments at LUCIA and PUMA beamlines at SOLEIL.

This paper reports on a new demonstrator of multi-element germanium detector for X-ray Absorption Spectroscopy (XAS) applications, with an optimized front-end electronics. The new front-end board can be easily scalable to a large number of channels and has been built in ceramics material for a better vacuum compatibility and temperature homogeneity in germanium crystal. The demonstrator performance has been simulated with a complete simulation chain based on Allpix Square framework and SolidStateDetector software. First simulation and experimental results of the new demonstrator are reported.

The use of cell-free scaffolds for the regeneration of clinically relevant volumes of soft tissue has been challenged, particularly in the case of synthetic biomaterials, by the difficulty of reconciling the manufacturing and biological performance requirements. Here, we investigated in vivo the importance of biomechanical and biochemical cues for conditioning the 3D regenerative microenvironment towards soft tissue formation. In particular, we evaluated the adipogenesis changes related to 3D mechanical properties by creating a gradient of 3D microenvironments with different stiffnesses using 3D Poly(Urethane-Ester-ether) PUEt scaffolds. Our results showed a significant increase in adipose tissue proportions while decreasing the stiffness of the 3D mechanical microenvironment. This mechanical conditioning effect was also compared with biochemical manipulation by loading extracellular matrices (ECMs) with a PPAR-γ activating molecule. Notably, results showed mechanical and biochemical conditioning equivalency in promoting adipose tissue formation in the conditions tested, suggesting that adequate mechanical signaling could be sufficient to boost adipogenesis by influencing tissue remodeling. Overall, this work could open a new avenue in the design of synthetic 3D scaffolds for microenvironment conditioning towards the regeneration of large volumes of soft and adipose tissue, with practical and direct implications in reconstructive and cosmetic surgery.

In this paper, the development of a tri-axial high-g shock sensor based on ST ThELMA (Thick Epitaxial Layer for Micro-gyroscopes and Accelerometers) MEMS (Micro Electro-Mechanical Sensors) technology is presented. We provide a comprehensive overview on shock sensing by comparing the current solutions available on the market and in the literature with the proposed design. From an extensive measurement campaign using a first prototype and reference sensors, design guidelines were extracted. These include: required full scale, minimum output data rate, bandwidth range and operation mode, for a dedicated high-g sensor for the mass market. Additionally, we briefly illustrate how this sensor can be coupled with a low-g accelerometer to add value in inertial systems.

A new operational mode of a frequency-modulated (FM) accelerometer for simultaneously improved full-scale, stability and bandwidth is presented. The system relies on a continuous sinusoidal modulation of the electromechanical configuration of a single resonator, which gradually reverses the sign of its frequency sensing: as a consequence, a secondary amplitude-modulation (AM) is superimposed to the primary FM effect. The following demodulations automatically cancel temperature-related drifts of the resonator frequency. The accelerometer is coupled to an integrated circuit that embeds an analog oscillator and a frequency digitization stage, with an overall consumption of 148 μA. A sub-80-μg/K drift coefficient and, at the same time, a sub-0.25% linearity error over 42 g of input acceleration are demonstrated. The achievable bandwidth is half of the chosen AM modulation frequency.

The work presents and characterizes a frequency digitization circuit used in a multi-parameter, multi-axis inertial measurement unit wholly based on frequency modulated (FM) sensors. With a low quantization noise of 35μHZms at 100-Hz output data rate, and a linear full-scale of 1 kHz, the proposed frequency to digital converter (FDC) achieves 149 dB of dynamic range, referred to a 50 Hz sensing bandwidth. The circuit operation is successfully demonstrated on both Lissajous FM gyroscopes and time-switched FM accelerometers, on both in-plane and out-of-plane sensing axes.

The ability to cryopreserve natural killer (NK) cells has a significant potential in modern cancer immunotherapy. Current cryopreservation protocols cause deterioration in NK cell viability and functionality. This work reports the preservation of human cytokine-activated NK cell viability and function following cryopreservation using a cocktail of biocompatible bioinspired cryoprotectants (i.e., dextran and carboxylated ε-poly-L-lysine). Results demonstrate that the recovered NK cells after cryopreservation and rewarming maintain their viability immediately after thawing at a comparable level to control (dimethyl sulfoxide-based cryopreservation). Although, their viability drops in the first day in culture compared to controls, the cells grow back to a comparable level to controls after 1 week in culture. In addition, the anti-tumor functional activity of recovered NK cells demonstrates higher cytotoxic potency against leukemia cells compared to control. This approach presents a new direction for NK cell preservation, focusing on function and potentially enabling storage and distribution for cancer immunotherapy.

The development of new generations of synchrotron light sources aims at increasing their beam in term of flux and brightness. To cope with extremely high-brilliance sources, fluorescence detectors must go beyond their nowadays maximum throughput while keeping almost unchanged the performance. This paper has been carried out within the framework of the ARDESIA (ARray of DEtectors for Spectroscopy and Imaging Applications) project, whose primary aim is to develop a spectrometer with count-rate capability for applications like Xray absorption spectroscopy (XAS) and X-ray fluorescence (XRF). ARDESIA is a Silicon Drift Detector (SDD)-based, multichannel X-ray spectrometer, optimized for synchrotron applications requiring a high-count rate (>1Mcps per channel) and a high-resolution (e.g. below 150 eV of Full Width Half Maximum at peaking times faster than 200 ns) for X-ray fluorescence detection. This paper describes improvements made for the ARDESIA spectrometer on detection efficiency and overall counting rate capability to better match requirements of synchrotron experiments. These improvements have been obtained by increasing the number of channels, from 4 to 16, and the SDD thickness from 450 mu m to 800 mu m and 1000 mu m. The new detection module and the new complete spectrometer are described in detail. The first 16-channel detection module prototype has been developed with an average resolution of 128 eV at the Mn-K alpha at long peaking times (i.e. > 2 mu s) and 183.5 eV at short peaking time (i.e. 32 ns). Then, the qualification of the 4-channel 1mm-thick detector at the PETRA (Positron-Elektron-Tandem-Ring-Anlage) P65 beamline in DESY (Deutsches Elektronen-Synchrotron) is reported.

The replication of the complex structure and three dimensional (3-D) interconnectivity of neurons in the brain is a great challenge. A few 3-D neuronal patterning approaches have been developed to mimic the cell distribution in the brain but none have demonstrated the relationship between 3-D neuron patterning and network connectivity. Here, we used photolithographic crosslinking to fabricate in vitro 3-D neuronal structures with distinct sizes, shapes or interconnectivities, i.e., milli-blocks, micro-stripes, separated micro-blocks and connected micro-blocks, which have spatial confinement from "Z" dimension to "XYZ" dimension. During a 4-week culture period, the 3-D neuronal system has shown high cell viability, axonal, dendritic, synaptic growth and neural network activity of cortical neurons. We further studied the calcium oscillation of neurons in different 3-D patterns and used signal processing both in Fast Fourier Transform (FFT) and time domain (TD) to model the fluorescent signal variation. We observed that the firing frequency decreased as the spatial confinement in 3-D system increased. Besides, the neuronal synchronization significantly decreased by irregularly connecting micro-blocks, indicating that network connectivity can be adjusted by changing the linking conditions of 3-D gels. Earlier works showed the importance of 3-D culture over 2-D in terms of cell growth. Here, we showed that not only 3-D geometry over 2-D culture matters, but also the spatial organization of cells in 3-D dictates the neuronal firing frequency and synchronicity.

This paper reports the developments toward an integrated, tri-axial, frequency-modulated, consumer-grade, and microelectromechanical system (MEMS) gyroscope. A custom low-power (160 μA), low-phase-noise integrated circuit is designed specifically for frequency-modulated operation. Both yaw- and pitch-rate sensing systems are demonstrated by coupling the circuit with two novel micromachined structures fabricated with a 24- μm-thick industrial process. In operation, both gyroscopes show a repeatable and stable scale factor, with less than 0.55% of part-to-part variability, obtained with no any calibration, and 35 ppm/ $^{\circ }$C of variability over a 25–70 $^{\circ }$C temperature range.

Organized networks are common in nature showing specific tissue micro-architecture, where cells can be found isotropically or anisotropically distributed in characteristic arrangements and tissue stiffness. However, when addressing an in vitro tissue model, it is challenging to grant control over mechanical properties while achieving anisotropic porosity of polymeric networks, especially in three-dimensional systems (3-D). While progress was achieved organizing cells in two-dimension (2-D), fabrication methods for aligned networks in 3-D are limited. Here, we describe the use of a biomimetic extra-cellular matrix system allowing programming of anisotropic structures into precisely advancing pore diameters in 3-D. Using control over polymeric composition, crosslinking directionality and freezing gradient dynamics, we revealed a mechanism to top-down biofabricate 3-D structures with tunable micro-porosity capable of directing cellular responses at millimeter scale such as axonal anisotropic outgrowth that is a unique characteristic of the brain cortex. Further, we showed the unique integration of this method with a microfluidic system establishing a neural-endothelial heterotypic conjugation, which can potentially be broadly applied to multiple organ systems.

Fat grafting is emerging as a promising alternative to silicon implants in breast reconstruction surgery. Unfortunately, this approach does not provide a proper mechanical support and is affected by drawbacks such as tissue resorption and donor site morbidity. Synthetic scaffolds can offer a valuable alternative to address these challenges, but poorly recapitulate the biochemical stimuli needed for tissue regeneration. Here, we aim at combining the positive features of a structural, synthetic polymer to an engineered, devitalized extracellular matrix (ECM) to generate a hybrid construct that can provide a mix of structural and biological stimuli needed for adipose tissue regeneration. A RGD-mimetic synthetic scaffold OPAAF, designed for soft tissue engineering, was decorated with ECM deposited by human adipose stromal cells (hASCs). The adipoinductive potential of the hybrid ECM-OPAAF construct was validated in vitro, by culture with hASC in a perfusion bioreactor system, and in vivo, by subcutaneous implantation in nude mouse. Our findings demonstrate that the hybrid ECM-OPAAF provides proper mechanical support and adipoinductive stimuli, with potential applicability as off-the-shelf material for adipose tissue reconstruction.STATEMENT OF SIGNIFICANCE:In this study we combined the functionalities of a synthetic polymer with those of an engineered and subsequently devitalized extracellular matrix (ECM) to generate a hybrid material for adipose tissue regeneration. The developed hybrid ECM-OPAAF was demonstrated to regulate human adipose stromal cells adipogenic commitment in vitro and adipose tissue infiltration in vivo. Our findings demonstrate that the hybrid ECM-OPAAF provide proper mechanical support and adipoinductive stimuli and represents a promising off-the-shelf material for adipose tissue reconstruction. We believe that our approach could offer an alternative strategy for adipose tissue reconstruction in case of mastectomy or congenital abnormalities, overcoming the current limitations of autologous fat based strategies such as volume resorption and donor site morbidity.

The purpose of this chapter is to describe the working principle of the microelectromechanical systems (MEMS) devices used in motion sensors and to consider their level of sophistication, performance limits, and future evolution. The integration of a multiparameter sensor in a single unit can increase the smartness of the device and enables the implementation of new functionalities in existing electronic systems. MEMS accelerometers, gyroscopes, and magnetometers are discussed in detail, as they represent the core devices for the development of a high-precision inertial measurement unit. At the end of the chapter, consideration is given to the evolution of these units integrating new MEMS devices for added functionalities, such as pressure sensing or proximity measurements.

Reconstructive treatment after trauma and tumor resection would greatly benefit from an effective soft tissue regeneration. The use of cell-free scaffolds for adipose tissue regeneration in vivo is emerging as an attractive alternative to tissue-engineered constructs, since this approach avoids complications due to cell manipulation and lack of synchronous vascularization. In this study, we developed a biodegradable polyurethane-based scaffold for soft tissue regeneration, characterized by an exceptional combination between softness and resilience. Exploring the potential as a cell-free scaffold required profound understanding of the impact of its intrinsic physico-chemical properties on the biological performance in vivo. We investigated the effect of the scaffold's hydrophilic character, degradation kinetics, and internal morphology on (i) the local inflammatory response and activation of MGCs (foreign body response); (ii) its ability to promote rapid vascularisation, cell infiltration and migration through the scaffold over time; and (iii) the grade of maturation of the newly formed tissue into vascularized soft tissue in a murine model. The study revealed that soft tissue regeneration in vivo proceeded by gradual infiltration of undifferentiated mesenchymal cells though the periphery toward the center of the scaffold, where the rapid formation of a functional and well-formed vascular network supported cell viability overtime. (C) 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

This paper describes the working principle, the design, and the characterization of a three-axis frequency-modulated MEMS accelerometer, in which the differential frequency readout is performed through a novel time-switched approach. The proposed methodology is based on a double sampling of the oscillation frequency of a single resonator, consecutively biased in two different configurations in time. This technique enables to avoid offset thermal drift contributions typical of differential resonant accelerometers based on two distinct resonators with unavoidable mismatch in the temperature coefficient of frequency (TCf). Alternatively, a residual TCf offset drift component can be tuned to counterbalance other drift sources (e.g., stress-related), allowing a complete cancellation of the zero-g-offset (ZGO) thermal drift. Experiments on various samples report repeatable sub- $50~\mu \text{g}$ /K thermal drift without post-acquisition corrections, with a full-scale higher than $32~g$ at a $100~\mu \text{g}/\sqrt {\text {Hz}}$ consumer-grade resolution. [2018-0089]

Abstract Sensors as devices can be considered the most advanced microelectronics systems built by connecting different types of microchips as micro-mechanical structure (MEMS) and Application Specific Integrated Circuit (ASIC). These Systems in Package (SiP) use mostly an epoxy resin material whose major reliability concern is the moisture absorption after humidity exposure so that the electrical interconnections between the dies become surrounded by a non-waterproof material. This article describes how the real resin morphology influences the electrical signals provided by a MEMS to an ASIC in an inertial sensor SiP. In particular, the study is focused on the pads area of the MEMS, where a large surface of polysilicon is in direct contact with the resin. As the epoxy structure close to the above regions may be affected by a non-homogeneous distribution of fillers, the compound humidity sensitivity may locally increase and the electrical properties may be conditioned in the same way. The goal of this study is to define a suitable method to quantify and characterize the local change of the resin properties after moisture absorption. After deeply analyzing the results of the standard electronics measurements methods an electrochemical approach has been selected as the best appropriate one to match the physical reality.

The work presents principle of operation, design and test of a novel z-axis MEMS accelerometer realized through a single resonator, in which the differential readout is achieved sampling the two resonant frequency values obtained alternatively biasing suitable tuning electrodes in subsequent time intervals. An electronic oscillator sustains the MEMS resonator, providing a low-phase-noise signal to a frequency counter. The accelerometer shows a sensitivity of 1.3Hz/g, with linearity error lower than 1% up to 15g and a consumer-grade resolution of 160μg /√Hz. The key-feature of the proposed inertial sensor is that the ZGO (zero-g offset) thermal drift can be conceptually nulled. Preliminary demonstrations report values lower than 100 μg / K without post-acquisition compensation.