Ultra-Stable and Robust Response to X-Rays in 2D Layered Perovskite Micro-Crystalline Films Directly Deposited on Flexible Substrate

2D layered hybrid perovskites have recently attracted an increasing interest as active layers in LEDs and UV–Vis photodetectors. 2D perovskites crystallize in a natural self-assembled quantum well-like structure and possess several interesting features among which low-temperature (<100 °C) synthesis and low defect density. Here are presented solid-state ionizing radiation direct detectors based on the 2D layered hybrid perovskite PEA2PbBr4 (PEA = C6H5C2H4NH3+) deposited from solution using scalable techniques and directly integrated onto a pre-patterned flexible substrate in the form of micro-crystalline films displaying crystal-like behavior, as evidenced by the ultra-fast (sub-microsecond) and good detection performances under UV light. The effective detection of X-rays (up to 150 kVp) is demonstrated with sensitivity values up to 806 µC Gy−1 cm−2 and Limit of Detection of 42 nGy s−1, thus combining the excellent performance for two relevant figures of merit for solid-state detectors. Additionally, the tested devices exhibit exceptionally stable response under constant irradiation and bias, assessing the material robustness and the intimate electrical contact with the electrodes. PEA2PbBr4 micro-crystalline films directly grown on flexible pre-patterned substrate open the way for large-area solid-state detectors working at low radiation flux for ultra-fast X-ray imaging and dosimetry

Morphology and mobility as tools to control and unprecedentedly enhance X-ray sensitivity in organic thin-films

Organic semiconductor materials exhibit a great potential for the realization of large-area solution-processed devices able to directly detect high-energy radiation. However, only few works investigated on the mechanism of ionizing radiation detection in this class of materials, so far. In this work we investigate the physical processes behind X-ray photoconversion employing bis-(triisopropylsilylethynyl)-pentacene thin-films deposited by bar-assisted meniscus shearing. The thin film coating speed and the use of bis-(triisopropylsilylethynyl)-pentacene:polystyrene blends are explored as tools to control and enhance the detection capability of the devices, by tuning the thin-film morphology and the carrier mobility. The so-obtained detectors reach a record sensitivity of 1.3 \ub7 104 \ub5C/Gy\ub7cm2, the highest value reported for organic-based direct X-ray detectors and a very low minimum detectable dose rate of 35 \ub5Gy/s. Thus, the employment of organic large-area direct detectors for X-ray radiation in real-life applications can be foreseen

Designing Ultraflexible Perovskite X-Ray Detectors through Interface Engineering

X-ray detectors play a pivotal role in development and advancement of humankind, from far-reaching impact in medicine to furthering the ability to observe distant objects in outer space. While other electronics show the ability to adapt to flexible and lightweight formats, state-of-the-art X-ray detectors rely on materials requiring bulky and fragile configurations, severely limiting their applications. Lead halide perovskites is one of the most rapidly advancing novel materials with success in the field of semiconductor devices. Here, an ultraflexible, lightweight, and highly conformable passively operated thin film perovskite X-ray detector with a sensitivity as high as 9.3 ± 0.5 µC Gy−1 cm−2 at 0 V and a remarkably low limit of detection of 0.58 ± 0.05 μGy s−1 is presented. Various electron and hole transporting layers accessing their individual impact on the detector performance are evaluated. Moreover, it is shown that this ultrathin form-factor allows for fabrication of devices detecting X-rays equivalently from front and back side

A novel multidrug‐resistant cell line from an italian intrahepatic cholangiocarcinoma patient

Chemotherapy resistance is a relevant clinical issue in tumor treatment, in particular in biliary tract carcinoma (BTC), for which there are no effective therapies, neither in the first nor in the second line. The development of chemoresistant cell lines as experimental models to investigate the mechanisms of resistance and identify alternative druggable pathways is mandatory. In BTC, in which genetics and biological behavior depend on the etiology, ethnicity, and anatomical site of origin, the creation of models that better recapitulate these characteristics is even more crucial. Here we have established and characterized an intrahepatic cholangiocarcinoma (iCCA) cell line derived from an Italian patient, called 82.3. Cells were isolated from a patient-derived xenograft (PDX) and, after establishment, immunophenotypic, biological, genetic, molecular characteristics, and tumorigenicity in vivo in NOD/SCID mice were investigated. 82.3 cells exhibited epithelial morphology and cell markers (EPCAM, CK7, and CK19); they also expressed different cancer stem markers (CD44, CD133, CD49b, CD24, Stro1, PAX6, FOXA2, OCT3/4), α–fetoprotein and under anchorage-independent and serum-free conditions were capable of originating cholangiospheres. The population doubling time was approximately 53 h. In vitro, they demonstrated a poor ability to migrate; in vivo, 82.3 cells retained their tumorigenicity, with a long latency period (16 weeks). Genetic identity using DNA fingerprinting analysis revealed 16 different loci, and the cell line was characterized by a complex hyperdiploid karyotype. Furthermore, 82.3 cells showed cross-resistance to gemcitabine, 5-fluorouracil, carboplatin, and oxaliplatin; in fact, their genetic profile showed that 60% of genes (n = 168), specific for drug resistance and related to the epithelial-mesenchymal transition, were deregulated in 82.3 cells compared to a control iCCA cell line sensitive to chemotherapeutics. RNA sequencing analysis revealed the enrichment for genes associated with epithelial to mesenchymal transition (EMT), vasculature development, and extracellular matrix (ECM) remodeling, underlining an aggressive phenotype. In conclusion, we have created a new iCCA cell line of Caucasian origin: this could be exploited as a preclinical model to study drug resistance mechanisms and to identify alternative therapies to improve the prognosis of this tumor type

Pazopanib and trametinib as a synergistic strategy against osteosarcoma: Preclinical activity and molecular insights

Receptor tyrosine kinases (RTKs) inhibitors’ activity in advanced osteosarcoma is significant but short-lived. To prevent or at least delay drug resistance, we explored a vertical inhibition by combining drugs acting at different levels of the RTK pathways (pazopanib + trametinib). We studied pazopanib + trametinib antitumor activity both in vitro and in vivo (MNNG-HOS and KHOS xenografts in NOD/SCID mice) investigating the molecular mechanisms and potential escapes. The involvement of MAPK-PI3K pathways was validated by Nanostring technology, western blot and by silencing/overexpression experiments. Pazopanib targets were expressed on seven osteosarcoma cell lines and their pathways were activated. Pazopanib + trametinib exhibited synergistic antitumor activity by inducing apoptosis and inhibiting ERK1/2 and Akt. In vivo antitumor activity was shown in osteosarcoma-bearing mice. The drug combination significantly down-modulated RTK Ephrin Type-A Receptor 2 (EphA2) and Interleukin-7 Receptor (IL-7R), whereas induced mitogen-activated protein-kinase kinase (MAPKK) MEK6. EphA2 silencing significantly reduced osteosarcoma cell proliferation and migration, while impeding MEK6 up-regulation in the treated cells significantly increased the antitumor effect of the studied drugs. Moreover, the up-regulation of MEK6 reduced combination activity. Pazopanib + trametinib demonstrated synergistic antitumor effects in osteosarcoma models through ERK and Akt inhibition and EphA2 and IL-7R down-modulation. MEK6 up-regulation might evoke escaping mechanism

Molecular Weight Tuning of Organic Semiconductors for Curved Organic-Inorganic Hybrid X-Ray Detectors

Curved X-ray detectors have the potential to revolutionize diverse sectors due to benefits such as reduced image distortion and vignetting compared to their planar counterparts. While the use of inorganic semiconductors for curved detectors are restricted by their brittle nature, organic-inorganic hybrid semiconductors which incorporated bismuth oxide nanoparticles in an organic bulk heterojunction consisting of poly(3-hexylthiophene-2,5-diyl) (P3HT) and [6,6]-phenyl C71 butyric acid methyl ester (PC70BM) are considered to be more promising in this regard. However, the influence of the P3HT molecular weight on the mechanical stability of curved, thick X-ray detectors remains less well understood. Herein, high P3HT molecular weights (>40 kDa) are identified to allow increased intermolecular bonding and chain entanglements, resulting in X-ray detectors that can be curved to a radius as low as 1.3 mm with low deviation in X-ray response under 100 repeated bending cycles while maintaining an industry-standard dark current of mu C Gy(-1) cm(-2). This study identifies a crucial missing link in the development of curved detectors, namely the importance of the molecular weight of the polymer semiconductors used