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

Trap States Ruling Photoconductive Gain in Tissue-Equivalent, Printed Organic X-Ray Detectors

Organic semiconductors are excellent candidates for X-ray detectors that can adapt to new applications, with unique properties including mechanical flexibility and the ability to cover large surfaces. Their chemical composition, primarily carbon and hydrogen, makes them human tissue equivalent in terms of radiation absorption. This is a highly desirable property for a radiation dosimeter to be employed in medical diagnostics and therapy, however a low-Z composition limits the absorption of ionizing radiation. The detection efficiency can be enhanced by considering the photoconductive gain (PG) effect, a significant contributor to the ionizing radiation detection mechanism in this class of materials. In this work, a process of controlled solution deposition by nozzle printing and crystallization of an organic semiconductor thin film is demonstrated whereby a flexible, arrayed thin-film X-ray detector with record X-ray sensitivities among flexible radiation detectors (S = (9.0 +/- 0.4) x 10(7) mu C Gy(-1) cm(-3)) is developed. The excitonic peaks responsible for the activation of the PG effect are investigated and identified using a novel technique called photocurrent spectroscopy optical quenching, and the analysis of the changes in trap states is further demonstrated

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

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

Tissue Equivalent Curved Organic X-ray Detectors Utilizing High Atomic Number Polythiophene Analogues

Organic semiconductors are a promising material candidate for X-ray detection. However, the low atomic number (Z) of organic semiconductors leads to poor X-ray absorption thus restricting their performance. Herein, the authors propose a new strategy for achieving high-sensitivity performance for X-ray detectors based on organic semiconductors modified with high –Z heteroatoms. X-ray detectors are fabricated with p-type organic semiconductors containing selenium heteroatoms (poly(3-hexyl)selenophene (P3HSe)) in blends with an n-type fullerene derivative ([6,6]-Phenyl C71 butyric acid methyl ester (PC70BM). When characterized under 70, 100, 150, and 220 kVp X-ray radiation, these heteroatom-containing detectors displayed a superior performance in terms of sensitivity up to 600 ± 11 nC Gy−1 cm−2 with respect to the bismuth oxide (Bi2O3) nanoparticle (NP) sensitized organic detectors. Despite the lower Z of selenium compared to the NPs typically used, the authors identify a more efficient generation of electron-hole pairs, better charge transfer, and charge transport characteristics in heteroatom-incorporated detectors that result in this breakthrough detector performance. The authors also demonstrate flexible X-ray detectors that can be curved to a radius as low as 2 mm with low deviation in X-ray response under 100 repeated bending cycles while maintaining an industry-standard ultra-low dark current of 0.03 ± 0.01 pA mm−2